胃癌细胞RegⅠ基因内含子的顺式调控功能
|
摘要
研究背景和目的
人类RegⅠ(regenerating gene Ⅰ)基因是1个单拷贝基因,为Reg基因家族的1员,定位于2号染色体,由6个外显子和5个内含子组成。Reg蛋白的功能与抗凋亡因子、急性反应蛋白和神经细胞生长因子相似。近年的研究结果表明,RegⅠ蛋白在胃癌组织中高表达；Reg Ⅰ基因的表达与胃癌的分化程度、浸润性生长以及患者的预后均存在有相关性。
胃泌素是由胃和上段小肠粘膜的G细胞分泌的一种多肽类激素,通过与膜上的缩胆囊素-B/促胃液素受体特异性结合而刺激胃酸的分泌。胃泌素与胃上皮细胞的增殖、壁细胞和ECL细胞的数量增加均有非常密切的关系,而且在胃黏膜的恶性变过程中也起着非常重要的作用。前期的研究显示,胃泌素可通过上调RegⅠ基因的表达促进胃癌细胞的生长。但是,胃泌素上调Reg Ⅰ基因表达的分子机制尚不清楚。
真核细胞的基因表达由顺式作用元件(cis-acting element)和反式作用因子(trans-acting factor)相互作用而调控。顺式作用元件通常为非编码序列,可影响自身基因的表达活性。Reg Ⅰ基因内含子是否具有顺式调控功能?胃泌素能否对RegⅠ基因内含子的功能产生效应?前期的研究显示,胃癌细胞RegⅠ基因第2内含子具有顺式调控功能。在此基础上,本研究分别克隆人白细胞RegⅠ基因第1、3、4和5内含子,构建荧光素酶报告载体,转染SGC-7901胃癌细胞,检测荧光素酶活性,分析RegⅠ基因第1、3、4和5内含子的顺式调控功能。胃泌素孵育转染荧光素酶报告载体的胃癌细胞系,观察胃泌素对RegⅠ基因第1、3、4和5内含子的顺式调控功能的效应。
材料与方法
1.构建Reg Ⅰ基因第1、3、4和5内含子的萤光素酶报告载体应用PCR技术从人白细胞分别克隆RegⅠ基因的第1、3、4和5内含子,产物经SacⅠ/KpnⅠ双酶切后,将Reg Ⅰ基因第1、3、4和5内含子片段分别克隆入pbluescript IISK+载体,分别命名为S-intron1、SK-intron3、SK-intron4和SK-intron5。再分别亚克隆至萤光素酶报告载体pGL3-Basic,构建含Reg Ⅰ基因第1、3、4和5内含子的报告载体,分别命名为pGL3-intron1、pGL3-intron3, pGL3-intron4和pGL3-intron5。重组质粒经SacⅠ/KpnⅠ双酶切及测序鉴定。
2.转染培养胃癌细胞系SGC7901。应用脂质体LipofectamineTM2000,分3组进行转染：对照组,无质粒转染；实验对照组,转染pGL3-Basic;实验组,分别转染pGL3-intron1、pGL3-intron3、pGL3-intron4和pGL3-intron5。
3.荧光素酶活性检测加入1×107mol/L胃泌素孵育12h,提取细胞上清,Glomax荧光检测仪检测各组细胞胃泌素孵育前后荧光素酶活性：
4.统计学分析：实验数据均采用SPSS17.0统计软件进行分析。数据以均数士标准差表示,应用单因素方差分析进行组间数据差异比较,以P<0.05为差异有显著性。
结果
1.构建RegⅠ基因第1、3、4和5内含子萤光素酶报告载体：pGL3-intron1、 pGL3-intron3、pGL3-intron4和pGL3-intron5经KpnⅠ/SacⅠ双酶切后,琼脂糖凝胶电泳鉴定,插入片段长度与预期一致。DNA测序显示,其序列与GenBank报道一致,且插入方向正确。
2.荧光素酶活性检测：pGL3-intron1组、pGL3-intron3组、pGL3-intron4组、pGL3-intron5组和pGL3-Basic组荧光素酶活性分别为221.778±33.937、3386.556±228.544、4092.889±131.920、1256±77.444和185±14.526。实验组pGL3-intron1组与实验对照组无显著性差异(P>0.05),其余各组均明显高于实验对照组(P<0.05)
胃泌素孵育后,pGL3-intron1组、pGL3-intron3组、pGL3-intron4组、pGL3-intron5组和pGL3-Basic组荧光素酶活性分别为225.778±17.726、3244.333±193.602、4099±177.464、1757.667±330.856和184.889±13.242,与孵育前无显著性差异(P>0.05)。
结论
1.分别转染pGL3-intron1、pGL3-intron3、pGL3-intron4和pGL3-intron5后,胃癌细胞荧光素酶活性除转染pGL3-intron1组无明显改变外,其余各组均明显升高。结果表明,除第1内含子外,RegⅠ基因第3、4和5内含子具有顺式调控功能。
2.胃泌素孵育后,转染pGL3-intron3、pGL3-intron4和pGL3-intron5胃癌细胞荧光素酶活性无明显改变。结果表明,胃泌素对RegⅠ基因第3、4和5内含子的顺式调控功能无明显效应。
Background and Objective:
Human Reg Ⅰ (regenerating gene Ⅰ) gene is a single copy gene, one of the Reg gene family. The gene is located on chromosome2, composed of six exons and five introns. Function of Reg protein is similar to anti-apoptotic factor, acute reactive protein and nerve cell growth factor. Recent research results showed that the Reg Ⅰ protein was highly expressed in gastric carcinoma. Reg I gene expression was correlated with the differentiation degree, invasive growth of gastric cancer, and the prognosises of patients.
Gastrin is a type of polypeptide hormone secreted by G cells in the stomach and upper fragment of small intestinal. Gastrin stimulates gastric acid secretion via specific binding to the membrane cholecystokinin-B/gastrin receptor. Gastrin is correlated closely with proliferation of gastric epithelial cells, increase of the number of parietal cells and ECL cells, and also plays a very important role in the process of malignant transformation of gastric mucosa. Our previous study showed that gastrin could stimulate growth of gastric cancer cells by upregulating Reg Ⅰ gene expression. However, the molecular mechanis, of gastrin upregulaing Reg Ⅰ gene expression is still unclearly known.
Gene expression in eukaryotic cells is regulated by interaction of cis-acting element and trans-acting factor. Cis-acting elements are usually non-coding sequences, and can affect the activity of its own gene expression. Whether Reg I gene introns have cis-regulating function or not, and whether gastrin can affect the regulating function of Reg I gene introns or not? Our previous study showed that the2nd intron of Reg I gene had cis-regulating function in gastric cancer cells. On this basis, in this study Reg I gene1st,3rd,4th and5th introns were cloned from human leukocyte. The luciferase reporter vectors containing Reg I gene1st,3rd,4th and5th intron, respectively, were constructed. After transfection of gastric cancer line SGC7901, the luciferase activity was detected to analyze cis-regulating function of Reg I gene1st,3rd,4th and5th introns. Effects of gastrin on cis-regulating function of Reg I gene1st.3rd,4th and5th introns were analyzed by detection changes of luciferase activity after gastin incubation.
Materials and methods
1. Construction of luciferase reporter vectors containing Reg I gene intron1,3,4and5Reg I gene introns1,3,4and5were cloned from human leukocyte by using polymerase chain reaction (PCR). After Sac1/Kpn1digestion, the fragments of Reg I gene1,3,4and5intron were cloned into the pbluescript Ⅱ SK-vector, and named as SK-intron1, SK-intron3, SK-intron4and SK-intron5, respectively. Then, the fragments were subcloned into luciferase reporter vector pGL3-Basic to construct reporter vectors containing Reg I gene1,3,4and5intron, and named as pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively. The recombinant plasmids wereidentified by SacI/KpnI digestion and sequencing.
2. Transfection Gastric cancer cell line SGC7901was cultured and transfected with LipofectamineTM2000. The cells were divided into three groups:control group, no transfection; experimental control group, transfected with pGL3-Basic; experimental group, transfected with pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively.
3. Detection of luciferase activity The cells were incubated with gastrin at1×10-7mol/L final concentration for12h. The supernatants of cells were extracted, and the luciferase activity of each group with or without gastrin incubation was detected with Glomax fluorescence detector.
4. Statistical analysis The experimental data were analyzed with SPSS17.0statistical software. The data were expressed as mean±standard deviation. Comparison of the numerical difference between groups was analyzed with single factor analysis of variance. P<0.05was considered as significant difference.
Results
1. Construction of luciferase reporter vectors containing Reg I gene intron1,3,4and5After KpnI/SacI digestion, pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5were identificated by agarose gel electrophoresis. The results showed that the length of inserted fragments was similar to anticipation. The results of sequencing showed that the sequences of inserted fragments were consistent to those of GenBank reported, and the fragments were inserted in right direction.
2. Detection of luciferase activity The luciferase activity of group pGL3-intron1, group pGL3-intron3, group pGL3-intron4, group pGL3-intron5and group pGL3-basic was221.778±33.937,3386.556±228.544,4092.889±131.920,1256±77.444and185±14.526, respectively. There was no significant difference between the luciferase activity of group pGL3-intron1and that of pGL3-Basic (P>0.05), those of other three groups were significantly higher than that of pGL3-Basic (P<0.05).
After gastrin incubation, the luciferase activity of group pGL3-intron1, group pGL3-intron3, group pGL3-intron4, group pGL3-intron5and group pGL3-basic was225.778±17.726,3244.333±193.602,4099±177.4641757.667±330.856and184.889±13.242, respectively. Compared with before gastrin incubation, the luciferase activity of the four groups had no significant changes (P>0.05).
Conclusions
1. After transfection of pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively, the luciferase activity of gastric caner cells, except for the group pGL3-intron1, the other three groups increase significantlu. The results indicate that, except intron1, Reg I gene intron3,4and5has cis-regulating function.
2. After gastrin incubation, the luciferase activity of group pGL3-intron3, pGL3-intron4and pGL3-intron5has no significantly change. The results indicate that gastrin has no effects on cis-regulatory function of Reg I gene intron3,4and5.
人类RegⅠ(regenerating gene Ⅰ)基因是1个单拷贝基因,为Reg基因家族的1员,定位于2号染色体,由6个外显子和5个内含子组成。Reg蛋白的功能与抗凋亡因子、急性反应蛋白和神经细胞生长因子相似。近年的研究结果表明,RegⅠ蛋白在胃癌组织中高表达；Reg Ⅰ基因的表达与胃癌的分化程度、浸润性生长以及患者的预后均存在有相关性。
胃泌素是由胃和上段小肠粘膜的G细胞分泌的一种多肽类激素,通过与膜上的缩胆囊素-B/促胃液素受体特异性结合而刺激胃酸的分泌。胃泌素与胃上皮细胞的增殖、壁细胞和ECL细胞的数量增加均有非常密切的关系,而且在胃黏膜的恶性变过程中也起着非常重要的作用。前期的研究显示,胃泌素可通过上调RegⅠ基因的表达促进胃癌细胞的生长。但是,胃泌素上调Reg Ⅰ基因表达的分子机制尚不清楚。
真核细胞的基因表达由顺式作用元件(cis-acting element)和反式作用因子(trans-acting factor)相互作用而调控。顺式作用元件通常为非编码序列,可影响自身基因的表达活性。Reg Ⅰ基因内含子是否具有顺式调控功能?胃泌素能否对RegⅠ基因内含子的功能产生效应?前期的研究显示,胃癌细胞RegⅠ基因第2内含子具有顺式调控功能。在此基础上,本研究分别克隆人白细胞RegⅠ基因第1、3、4和5内含子,构建荧光素酶报告载体,转染SGC-7901胃癌细胞,检测荧光素酶活性,分析RegⅠ基因第1、3、4和5内含子的顺式调控功能。胃泌素孵育转染荧光素酶报告载体的胃癌细胞系,观察胃泌素对RegⅠ基因第1、3、4和5内含子的顺式调控功能的效应。
材料与方法
1.构建Reg Ⅰ基因第1、3、4和5内含子的萤光素酶报告载体应用PCR技术从人白细胞分别克隆RegⅠ基因的第1、3、4和5内含子,产物经SacⅠ/KpnⅠ双酶切后,将Reg Ⅰ基因第1、3、4和5内含子片段分别克隆入pbluescript IISK+载体,分别命名为S-intron1、SK-intron3、SK-intron4和SK-intron5。再分别亚克隆至萤光素酶报告载体pGL3-Basic,构建含Reg Ⅰ基因第1、3、4和5内含子的报告载体,分别命名为pGL3-intron1、pGL3-intron3, pGL3-intron4和pGL3-intron5。重组质粒经SacⅠ/KpnⅠ双酶切及测序鉴定。
2.转染培养胃癌细胞系SGC7901。应用脂质体LipofectamineTM2000,分3组进行转染：对照组,无质粒转染；实验对照组,转染pGL3-Basic;实验组,分别转染pGL3-intron1、pGL3-intron3、pGL3-intron4和pGL3-intron5。
3.荧光素酶活性检测加入1×107mol/L胃泌素孵育12h,提取细胞上清,Glomax荧光检测仪检测各组细胞胃泌素孵育前后荧光素酶活性：
4.统计学分析：实验数据均采用SPSS17.0统计软件进行分析。数据以均数士标准差表示,应用单因素方差分析进行组间数据差异比较,以P<0.05为差异有显著性。
结果
1.构建RegⅠ基因第1、3、4和5内含子萤光素酶报告载体：pGL3-intron1、 pGL3-intron3、pGL3-intron4和pGL3-intron5经KpnⅠ/SacⅠ双酶切后,琼脂糖凝胶电泳鉴定,插入片段长度与预期一致。DNA测序显示,其序列与GenBank报道一致,且插入方向正确。
2.荧光素酶活性检测：pGL3-intron1组、pGL3-intron3组、pGL3-intron4组、pGL3-intron5组和pGL3-Basic组荧光素酶活性分别为221.778±33.937、3386.556±228.544、4092.889±131.920、1256±77.444和185±14.526。实验组pGL3-intron1组与实验对照组无显著性差异(P>0.05),其余各组均明显高于实验对照组(P<0.05)
胃泌素孵育后,pGL3-intron1组、pGL3-intron3组、pGL3-intron4组、pGL3-intron5组和pGL3-Basic组荧光素酶活性分别为225.778±17.726、3244.333±193.602、4099±177.464、1757.667±330.856和184.889±13.242,与孵育前无显著性差异(P>0.05)。
结论
1.分别转染pGL3-intron1、pGL3-intron3、pGL3-intron4和pGL3-intron5后,胃癌细胞荧光素酶活性除转染pGL3-intron1组无明显改变外,其余各组均明显升高。结果表明,除第1内含子外,RegⅠ基因第3、4和5内含子具有顺式调控功能。
2.胃泌素孵育后,转染pGL3-intron3、pGL3-intron4和pGL3-intron5胃癌细胞荧光素酶活性无明显改变。结果表明,胃泌素对RegⅠ基因第3、4和5内含子的顺式调控功能无明显效应。
Background and Objective:
Human Reg Ⅰ (regenerating gene Ⅰ) gene is a single copy gene, one of the Reg gene family. The gene is located on chromosome2, composed of six exons and five introns. Function of Reg protein is similar to anti-apoptotic factor, acute reactive protein and nerve cell growth factor. Recent research results showed that the Reg Ⅰ protein was highly expressed in gastric carcinoma. Reg I gene expression was correlated with the differentiation degree, invasive growth of gastric cancer, and the prognosises of patients.
Gastrin is a type of polypeptide hormone secreted by G cells in the stomach and upper fragment of small intestinal. Gastrin stimulates gastric acid secretion via specific binding to the membrane cholecystokinin-B/gastrin receptor. Gastrin is correlated closely with proliferation of gastric epithelial cells, increase of the number of parietal cells and ECL cells, and also plays a very important role in the process of malignant transformation of gastric mucosa. Our previous study showed that gastrin could stimulate growth of gastric cancer cells by upregulating Reg Ⅰ gene expression. However, the molecular mechanis, of gastrin upregulaing Reg Ⅰ gene expression is still unclearly known.
Gene expression in eukaryotic cells is regulated by interaction of cis-acting element and trans-acting factor. Cis-acting elements are usually non-coding sequences, and can affect the activity of its own gene expression. Whether Reg I gene introns have cis-regulating function or not, and whether gastrin can affect the regulating function of Reg I gene introns or not? Our previous study showed that the2nd intron of Reg I gene had cis-regulating function in gastric cancer cells. On this basis, in this study Reg I gene1st,3rd,4th and5th introns were cloned from human leukocyte. The luciferase reporter vectors containing Reg I gene1st,3rd,4th and5th intron, respectively, were constructed. After transfection of gastric cancer line SGC7901, the luciferase activity was detected to analyze cis-regulating function of Reg I gene1st,3rd,4th and5th introns. Effects of gastrin on cis-regulating function of Reg I gene1st.3rd,4th and5th introns were analyzed by detection changes of luciferase activity after gastin incubation.
Materials and methods
1. Construction of luciferase reporter vectors containing Reg I gene intron1,3,4and5Reg I gene introns1,3,4and5were cloned from human leukocyte by using polymerase chain reaction (PCR). After Sac1/Kpn1digestion, the fragments of Reg I gene1,3,4and5intron were cloned into the pbluescript Ⅱ SK-vector, and named as SK-intron1, SK-intron3, SK-intron4and SK-intron5, respectively. Then, the fragments were subcloned into luciferase reporter vector pGL3-Basic to construct reporter vectors containing Reg I gene1,3,4and5intron, and named as pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively. The recombinant plasmids wereidentified by SacI/KpnI digestion and sequencing.
2. Transfection Gastric cancer cell line SGC7901was cultured and transfected with LipofectamineTM2000. The cells were divided into three groups:control group, no transfection; experimental control group, transfected with pGL3-Basic; experimental group, transfected with pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively.
3. Detection of luciferase activity The cells were incubated with gastrin at1×10-7mol/L final concentration for12h. The supernatants of cells were extracted, and the luciferase activity of each group with or without gastrin incubation was detected with Glomax fluorescence detector.
4. Statistical analysis The experimental data were analyzed with SPSS17.0statistical software. The data were expressed as mean±standard deviation. Comparison of the numerical difference between groups was analyzed with single factor analysis of variance. P<0.05was considered as significant difference.
Results
1. Construction of luciferase reporter vectors containing Reg I gene intron1,3,4and5After KpnI/SacI digestion, pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5were identificated by agarose gel electrophoresis. The results showed that the length of inserted fragments was similar to anticipation. The results of sequencing showed that the sequences of inserted fragments were consistent to those of GenBank reported, and the fragments were inserted in right direction.
2. Detection of luciferase activity The luciferase activity of group pGL3-intron1, group pGL3-intron3, group pGL3-intron4, group pGL3-intron5and group pGL3-basic was221.778±33.937,3386.556±228.544,4092.889±131.920,1256±77.444and185±14.526, respectively. There was no significant difference between the luciferase activity of group pGL3-intron1and that of pGL3-Basic (P>0.05), those of other three groups were significantly higher than that of pGL3-Basic (P<0.05).
After gastrin incubation, the luciferase activity of group pGL3-intron1, group pGL3-intron3, group pGL3-intron4, group pGL3-intron5and group pGL3-basic was225.778±17.726,3244.333±193.602,4099±177.4641757.667±330.856and184.889±13.242, respectively. Compared with before gastrin incubation, the luciferase activity of the four groups had no significant changes (P>0.05).
Conclusions
1. After transfection of pGL3-intron1, pGL3-intron3, pGL3-intron4and pGL3-intron5, respectively, the luciferase activity of gastric caner cells, except for the group pGL3-intron1, the other three groups increase significantlu. The results indicate that, except intron1, Reg I gene intron3,4and5has cis-regulating function.
2. After gastrin incubation, the luciferase activity of group pGL3-intron3, pGL3-intron4and pGL3-intron5has no significantly change. The results indicate that gastrin has no effects on cis-regulatory function of Reg I gene intron3,4and5.
引文
1. Henwood M, Clarke PA, Smith AM, et al. Expression of gastrin in developing gastric adenocarcinoma [J]. Br J Surg,2001,88 (4):564-568
2.高文和,王俊平.胃泌素及其受体拮抗剂对BGC2823细胞骨架微丝结构的作用[J].中华胃肠外科杂志,2001,4(2)：117-119
3. Violette S,Festor E, Pandrea-Vasile I, et al. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas [J]. Int J Cancer,2003,103(2):185-193
4.程珊,丁一,张钦宪.Reg Ⅰ在胃泌素促胃癌细胞体外增殖通路中的作用[J].解剖学报,2012,43(1)：63-67
5. Maniatis T, Reed R. An extensive network of coupling among gene expression machines [J]. Nature,2002,416(6880):499-506
6. Proudfoot NJ, Furger A, Dye MJ. Integrating mRNA processing with transcription [J]. Cell,2002,108(4):501-512
7. Orphanides G, Reinberg D. A unified theory of gene expression [J]. Cell,2002, 108(4):439-451
8. Maquat LE; Carmichael GG Quality control of mRNA function [J]. Cell 2001,104(2): 173-176
9. Zheng M, Storz G. Redox sensing by prokaryotic transcription factors [J]. Biochem Pharmacol,2000,59(1):1-6
10. Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer [J]. Chem Biol Interact,2006,160(1):1-40.
11. Lee JH, Youn GH, Kim BC, et al. An oxidative stress-specific bacterial cell array chip for toxicity analysis [J]. Biosens Bioelectron,2007,22(9-10):2223-2229
12. Haridas V, Kim SO, Xishimura G, et al. Avicinylation (thioesterification):a protein modification that can regulate the response to oxidative and nitrosative stress [J]. Proc Natl Acad Sci USA,2005,102(29):10088-10093
13. Girousse A, Tavernier G, Tiraby C, et al. Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences [J]. Diabetologia,2009,52(8):1638-1646
14. Fang H, Wang A, Gao B, et al. The regulatory effect of the first intron and 3'-regulatory region of ovalbumin gene on transgene expression [J]. Sheng Wu Gong Cheng Xue Bao,2008,24(2):333-338
15. Kleinschmidt AM, Nassiri M, Stitt MS, et al. Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice [J]. J Biol Chem,2008,283(5):2741-2750
16. Liu H, Zheng H, Duan Z, et al. LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells [J]. Mol Cancer,2009,8: 92
17. Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine Secreted phosphoprotein 1 gene: allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol,2009,10:96
18. Bianchi M, Crinelli R, Giacomini E, et al. A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene [J]. Gene,2009,448(1):88-101
19. Haddad-Mashadrizeh A, Zomorodipour A, Izadpanah M, et al. A systematic study of the function of the human beta-globin introns on the expression of the human coagulation factor IX in cultured Chinese hamster ovary cells [J]. J Gene Med, 2009,11(10):941-950
20. Ott CJ, Suszko M, Blackledge NP, et al. A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter [J]. J Cell Mol Med,2009,13(4):680-692
21. Makkonen H. Kauhanen M, Paakinaho V, et al. Long-range activation of FKBP51 transcription by the androgen receptor via distal intronic enhancers [J]. Nucleic Acids Res,2009,37(12):4135-4148
22. Xue J, Thippegowda PB, Hu G, et al. NF-kappaB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-kappaB site in the ICAM-1 gene [J]. Physiol Genomics,2009,38(1):42-53
23. Tsuji-Takayama K, Suzuki M, Yamamoto M, et al. The production of IL-10 by human regulatory T cells is enhanced by IL-2 through a STAT5-responsive intronic enhancer in the IL-10 locus [J]. J Immunol,2008,181(6):3897-3905
24. Chen JJ, Chou CW, Chang YF, et al. Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5:involvement of NF-kappa B and reactive oxygen species-mediated p53 activation [J]. J Immunol 2008,180(12):8030-8039
25. Blount AL, Vaughan JM, Vale WW, et al. A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene [J]. J Biol Chem,2008,283(11):7016-7026
26. Fukui H. Kinoshita Y, Maekawa T, et al. Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats [J]. Gastroenterology,1998,115(6):1483-1493
27. Ashcroft FJ, Varro A. Dimaline R, et al. Control of expression of the lectin-like protein Reg-1 by gastrin:role of the Rho family GTPase RhoA and a C-rich promoter element [J]. Biochem J,2004,381(Pt 2):397-403
28. Steele IA, Dimaline R, Pritchard DM, et al. Helicobacter and gastrin stimulate Regl expression in gastric epithelial cells through distinct promoter elements [J]. Am J Physiol Gastrointest Liver Physiol,2007,293(1):G347-354
1. Girousse A, Tavernier G, Tiraby C, et al. Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences [J]. Diabetologia,2009,52(8):1638-1646
2. Choi JW, Park CS, Hwang M, et al. A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli [J]. J Allergy Clin Immunol,2008,122(6):1119-1126
3. Delaloy C, Elvira-Matelot E, Clemessy M, et al. Deletion of WNK1 first intron results in misregulation of both isoforms in renal and extrarenal tissues [J]. Hypertension,2008,52(6):1149-1154
4. Fang H, Wang A, Gao B, et al. The regulatory effect of the first intron and 3'-regulatory region of ovalbumin gene on transgene expression [J]. Sheng Wu Gong Cheng Xue Bao,2008,24(2):333-338
5. Feng W, Huang J, Zhang J, et al. Identification and analysis of a conserved Tcfap2a intronic enhancer element required for expression in facial and limb bud mesenchyme [J]. Mol Cell Biol,2008,28(1):315-325
6. Kleinschmidt A M. Nassiri M, Stitt MS, et al. Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice [J]. J Biol Chem,2008,283(5):2741-2750
7. Liu H, Zheng H, Duan Z, et al. LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells [J]. Mol Cancer,2009,8:92
8. Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine Secreted phosphoprotein 1 gene: allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol.2009,10:96
9. Bianchi M, Crinelli R, Giacomini E, et al. A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene [J]. Gene,2009,448(1):88-101
10. Haddad-Mashadrizeh A, Zomorodipour A, Izadpanah M, et al. A systematic study of the function of the human beta-globin introns on the expression of the human coagulation factor IX in cultured Chinese hamster ovary cells [J]. J Gene Med, 2009,11(10):941-950
11. Ott CJ, Suszko M, Blackledge NP, et al. A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter [J]. J Cell Mol Med 2009,13(4):680-692
12. Makkonen H, Kauhanen M, Paakinaho V, et al. Long-range activation of FKBP51 transcription by the androgen receptor via distal intronic enhancers [J]. Nucleic Acids Res,2009,37(12):4135-4148
13.Xue J, Thippegowda PB, Hu G, et al. NF-kappaB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-kappaB site in the ICAM-1 gene [J]. Physiol Genomics,2009,38(1):42-53
14. Magklara A, Smith CL. A composite intronic element directs dynamic binding of the progesterone receptor and GATA-2 [J]. Mol Endocrinol,2009,23(1):61-73
15.,Hernandez-Saavedra D, McCord JM. Association of a new intronic polymorphism of the SOD2 gene (G1677T) with cancer [J]. Cell Biochem Funct, 2009,27(4):223-227
16. Bellizzi D, Covello G, Di Cianni F, et al. Identification of GATA2 and AP-1 Activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene [J]. Mol Cells,2009,28(2):87-92
17. Dutton JR, Antonellis A, Carney TJ, et al. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10[J]. BMC Dev Biol,2008,8:105
18. Tsuji-Takayama K, Suzuki M, Yamamoto M, et al. The production of IL-10 by human regulatory T cells is enhanced by IL-2 through a STAT5-responsive intronic enhancer in the IL-10 locus [J]. J Immunol,2008,181(6):3897-3905
19. Simon MP, Tournaire R, Pouyssegur J. The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1 [J]. J Cell Physiol,2008,217(3): 809-818
20. Kumar V, Becker T, Jansen S, et al. Expression levels of FAS are regulated through an evolutionary conserved element in intron 2, which modulates cystic fibrosis disease severity [J]. Genes Immun,2008,9(8):689-696
21. Chen JJ, Chou CW, Chang YF, et al. Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5:involvement of NF-kappa B and reactive oxygen species-mediated p53 activation [J]. J Immunol, 2008,180(12):8030-8039
22. Blount AL, Vaughan JM, Vale WW, et al. A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene. J Biol Chem. 2008,283(11):7016-26
23. Hejjas K, Kubinyi E, Ronai Z, et al. Molecular and behavioral analysis of the intron 2 repeat polymorphism in the canine dopamine D4 receptor gene [J]. Genes Brain Behav,2009,8(3):330-336
24. Zhu X, Asa SL, Ezzat S. Histone-acetylated control of fibroblast growth factor receptor 2 intron 2 polymorphisms and isoform splicing in breast cancer [J]. Mol Endocrinol,2009,23(9):1397-1405
25. Xiong L, Catoire H, Dion P. et al. MEIS1 intronic risk haplotype associated with restless legs syndrome affects its mRNA and protein expression levels [J]. Hum Mol Genet,2009,18(6):1065-1074
26. Poonkuzhali B, Lamba J, Strom S, et al. Association of breast cancer resistance protein/ABCG2 phenotypes and novel promoter and intron 1 single nucleotide polymorphisms [J]. Drug Metab Dispos,2008,36(4):780-795
27. Tiseo M, Capelletti M, De Palma G, et al. Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer [J].,2008,3(10):1104-1111
28. Buisine MP, Wacrenier A, Mariette C, et al. Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers [J]. World J Gastroenterol,2008,14(7):1053-1059
29. Kersting C, Agelopoulos K, Schmidt H, et al. Biological importance of a polymorphic CA sequence within intron 1 of the epidermal growth factor receptor gene (EGFR) in high grade central osteosarcomas [J]. Genes Chromosomes Cancer,2008,47(8):657-664
30. Sueoka-Aragane N, Imai K, Komiya K, et al. Exon 19 of EGFR mutation in relation to the CA-repeat polymorphism in intron 1 [J]. Cancer Sci,2008,99(6): 1180-1187
31. Soragni E, Herman D, Dent SY, et al. Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia [J]. Nucleic Acids Res,2008,36(19):6056-6665
32. Singh RK, Tapia-Santos A, Bebee TW, et al. Conserved sequences in the final intron of MDM2 are essential for the regulation of alternative splicing of MDM2 in response to stress [J]. Exp Cell Res,2009,315(19):3419-3432
33. Pros E, Femandez-Rodriguez J, Canet B, et al. Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations [J]. Hum Mutat,2009. 30(3):454-462
34. Holla L, Nakken S, Mattingsdal M, et al. Effects of intronic mutations in the LDLR gene on pre-mRNA splicing:Comparison of wet-lab and bioinformatics analyses [J]. Mol Genet Metab,2009,96(4):245-252
35. Yao Y, Schroder J, Nellaker C, et al. Elevated levels of human endogenous retrovirus-W transcripts in blood cells from patients with first episode schizophrenia [J].Genes Brain Behav,2008,7(1):103-112
36. Habara Y, Takeshima Y, Awano H, et al. In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by+1G-->A mutations in introns of the dystrophin gene [J]. J Med Genet,2009,46(8):542-547
37. Olsson A, Lind L, Thornell LE, et al. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect [J]. Hum Mol Genet,2008; 17(11):1666-1672
38. Xiao S, Tjostheim S, Sanelli T, et al. An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology [J]. J Neurosci,2008,28(8):1833-1840
2.高文和,王俊平.胃泌素及其受体拮抗剂对BGC2823细胞骨架微丝结构的作用[J].中华胃肠外科杂志,2001,4(2)：117-119
3. Violette S,Festor E, Pandrea-Vasile I, et al. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas [J]. Int J Cancer,2003,103(2):185-193
4.程珊,丁一,张钦宪.Reg Ⅰ在胃泌素促胃癌细胞体外增殖通路中的作用[J].解剖学报,2012,43(1)：63-67
5. Maniatis T, Reed R. An extensive network of coupling among gene expression machines [J]. Nature,2002,416(6880):499-506
6. Proudfoot NJ, Furger A, Dye MJ. Integrating mRNA processing with transcription [J]. Cell,2002,108(4):501-512
7. Orphanides G, Reinberg D. A unified theory of gene expression [J]. Cell,2002, 108(4):439-451
8. Maquat LE; Carmichael GG Quality control of mRNA function [J]. Cell 2001,104(2): 173-176
9. Zheng M, Storz G. Redox sensing by prokaryotic transcription factors [J]. Biochem Pharmacol,2000,59(1):1-6
10. Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer [J]. Chem Biol Interact,2006,160(1):1-40.
11. Lee JH, Youn GH, Kim BC, et al. An oxidative stress-specific bacterial cell array chip for toxicity analysis [J]. Biosens Bioelectron,2007,22(9-10):2223-2229
12. Haridas V, Kim SO, Xishimura G, et al. Avicinylation (thioesterification):a protein modification that can regulate the response to oxidative and nitrosative stress [J]. Proc Natl Acad Sci USA,2005,102(29):10088-10093
13. Girousse A, Tavernier G, Tiraby C, et al. Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences [J]. Diabetologia,2009,52(8):1638-1646
14. Fang H, Wang A, Gao B, et al. The regulatory effect of the first intron and 3'-regulatory region of ovalbumin gene on transgene expression [J]. Sheng Wu Gong Cheng Xue Bao,2008,24(2):333-338
15. Kleinschmidt AM, Nassiri M, Stitt MS, et al. Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice [J]. J Biol Chem,2008,283(5):2741-2750
16. Liu H, Zheng H, Duan Z, et al. LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells [J]. Mol Cancer,2009,8: 92
17. Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine Secreted phosphoprotein 1 gene: allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol,2009,10:96
18. Bianchi M, Crinelli R, Giacomini E, et al. A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene [J]. Gene,2009,448(1):88-101
19. Haddad-Mashadrizeh A, Zomorodipour A, Izadpanah M, et al. A systematic study of the function of the human beta-globin introns on the expression of the human coagulation factor IX in cultured Chinese hamster ovary cells [J]. J Gene Med, 2009,11(10):941-950
20. Ott CJ, Suszko M, Blackledge NP, et al. A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter [J]. J Cell Mol Med,2009,13(4):680-692
21. Makkonen H. Kauhanen M, Paakinaho V, et al. Long-range activation of FKBP51 transcription by the androgen receptor via distal intronic enhancers [J]. Nucleic Acids Res,2009,37(12):4135-4148
22. Xue J, Thippegowda PB, Hu G, et al. NF-kappaB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-kappaB site in the ICAM-1 gene [J]. Physiol Genomics,2009,38(1):42-53
23. Tsuji-Takayama K, Suzuki M, Yamamoto M, et al. The production of IL-10 by human regulatory T cells is enhanced by IL-2 through a STAT5-responsive intronic enhancer in the IL-10 locus [J]. J Immunol,2008,181(6):3897-3905
24. Chen JJ, Chou CW, Chang YF, et al. Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5:involvement of NF-kappa B and reactive oxygen species-mediated p53 activation [J]. J Immunol 2008,180(12):8030-8039
25. Blount AL, Vaughan JM, Vale WW, et al. A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene [J]. J Biol Chem,2008,283(11):7016-7026
26. Fukui H. Kinoshita Y, Maekawa T, et al. Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats [J]. Gastroenterology,1998,115(6):1483-1493
27. Ashcroft FJ, Varro A. Dimaline R, et al. Control of expression of the lectin-like protein Reg-1 by gastrin:role of the Rho family GTPase RhoA and a C-rich promoter element [J]. Biochem J,2004,381(Pt 2):397-403
28. Steele IA, Dimaline R, Pritchard DM, et al. Helicobacter and gastrin stimulate Regl expression in gastric epithelial cells through distinct promoter elements [J]. Am J Physiol Gastrointest Liver Physiol,2007,293(1):G347-354
1. Girousse A, Tavernier G, Tiraby C, et al. Transcription of the human uncoupling protein 3 gene is governed by a complex interplay between the promoter and intronic sequences [J]. Diabetologia,2009,52(8):1638-1646
2. Choi JW, Park CS, Hwang M, et al. A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli [J]. J Allergy Clin Immunol,2008,122(6):1119-1126
3. Delaloy C, Elvira-Matelot E, Clemessy M, et al. Deletion of WNK1 first intron results in misregulation of both isoforms in renal and extrarenal tissues [J]. Hypertension,2008,52(6):1149-1154
4. Fang H, Wang A, Gao B, et al. The regulatory effect of the first intron and 3'-regulatory region of ovalbumin gene on transgene expression [J]. Sheng Wu Gong Cheng Xue Bao,2008,24(2):333-338
5. Feng W, Huang J, Zhang J, et al. Identification and analysis of a conserved Tcfap2a intronic enhancer element required for expression in facial and limb bud mesenchyme [J]. Mol Cell Biol,2008,28(1):315-325
6. Kleinschmidt A M. Nassiri M, Stitt MS, et al. Sequences in intron 51 of the von Willebrand factor gene target promoter activation to a subset of lung endothelial cells in transgenic mice [J]. J Biol Chem,2008,283(5):2741-2750
7. Liu H, Zheng H, Duan Z, et al. LMP1-augmented kappa intron enhancer activity contributes to upregulation expression of Ig kappa light chain via NF-kappaB and AP-1 pathways in nasopharyngeal carcinoma cells [J]. Mol Cancer,2009,8:92
8. Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine Secreted phosphoprotein 1 gene: allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol.2009,10:96
9. Bianchi M, Crinelli R, Giacomini E, et al. A potent enhancer element in the 5'-UTR intron is crucial for transcriptional regulation of the human ubiquitin C gene [J]. Gene,2009,448(1):88-101
10. Haddad-Mashadrizeh A, Zomorodipour A, Izadpanah M, et al. A systematic study of the function of the human beta-globin introns on the expression of the human coagulation factor IX in cultured Chinese hamster ovary cells [J]. J Gene Med, 2009,11(10):941-950
11. Ott CJ, Suszko M, Blackledge NP, et al. A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter [J]. J Cell Mol Med 2009,13(4):680-692
12. Makkonen H, Kauhanen M, Paakinaho V, et al. Long-range activation of FKBP51 transcription by the androgen receptor via distal intronic enhancers [J]. Nucleic Acids Res,2009,37(12):4135-4148
13.Xue J, Thippegowda PB, Hu G, et al. NF-kappaB regulates thrombin-induced ICAM-1 gene expression in cooperation with NFAT by binding to the intronic NF-kappaB site in the ICAM-1 gene [J]. Physiol Genomics,2009,38(1):42-53
14. Magklara A, Smith CL. A composite intronic element directs dynamic binding of the progesterone receptor and GATA-2 [J]. Mol Endocrinol,2009,23(1):61-73
15.,Hernandez-Saavedra D, McCord JM. Association of a new intronic polymorphism of the SOD2 gene (G1677T) with cancer [J]. Cell Biochem Funct, 2009,27(4):223-227
16. Bellizzi D, Covello G, Di Cianni F, et al. Identification of GATA2 and AP-1 Activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene [J]. Mol Cells,2009,28(2):87-92
17. Dutton JR, Antonellis A, Carney TJ, et al. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10[J]. BMC Dev Biol,2008,8:105
18. Tsuji-Takayama K, Suzuki M, Yamamoto M, et al. The production of IL-10 by human regulatory T cells is enhanced by IL-2 through a STAT5-responsive intronic enhancer in the IL-10 locus [J]. J Immunol,2008,181(6):3897-3905
19. Simon MP, Tournaire R, Pouyssegur J. The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1 [J]. J Cell Physiol,2008,217(3): 809-818
20. Kumar V, Becker T, Jansen S, et al. Expression levels of FAS are regulated through an evolutionary conserved element in intron 2, which modulates cystic fibrosis disease severity [J]. Genes Immun,2008,9(8):689-696
21. Chen JJ, Chou CW, Chang YF, et al. Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5:involvement of NF-kappa B and reactive oxygen species-mediated p53 activation [J]. J Immunol, 2008,180(12):8030-8039
22. Blount AL, Vaughan JM, Vale WW, et al. A Smad-binding element in intron 1 participates in activin-dependent regulation of the follistatin gene. J Biol Chem. 2008,283(11):7016-26
23. Hejjas K, Kubinyi E, Ronai Z, et al. Molecular and behavioral analysis of the intron 2 repeat polymorphism in the canine dopamine D4 receptor gene [J]. Genes Brain Behav,2009,8(3):330-336
24. Zhu X, Asa SL, Ezzat S. Histone-acetylated control of fibroblast growth factor receptor 2 intron 2 polymorphisms and isoform splicing in breast cancer [J]. Mol Endocrinol,2009,23(9):1397-1405
25. Xiong L, Catoire H, Dion P. et al. MEIS1 intronic risk haplotype associated with restless legs syndrome affects its mRNA and protein expression levels [J]. Hum Mol Genet,2009,18(6):1065-1074
26. Poonkuzhali B, Lamba J, Strom S, et al. Association of breast cancer resistance protein/ABCG2 phenotypes and novel promoter and intron 1 single nucleotide polymorphisms [J]. Drug Metab Dispos,2008,36(4):780-795
27. Tiseo M, Capelletti M, De Palma G, et al. Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer [J].,2008,3(10):1104-1111
28. Buisine MP, Wacrenier A, Mariette C, et al. Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers [J]. World J Gastroenterol,2008,14(7):1053-1059
29. Kersting C, Agelopoulos K, Schmidt H, et al. Biological importance of a polymorphic CA sequence within intron 1 of the epidermal growth factor receptor gene (EGFR) in high grade central osteosarcomas [J]. Genes Chromosomes Cancer,2008,47(8):657-664
30. Sueoka-Aragane N, Imai K, Komiya K, et al. Exon 19 of EGFR mutation in relation to the CA-repeat polymorphism in intron 1 [J]. Cancer Sci,2008,99(6): 1180-1187
31. Soragni E, Herman D, Dent SY, et al. Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia [J]. Nucleic Acids Res,2008,36(19):6056-6665
32. Singh RK, Tapia-Santos A, Bebee TW, et al. Conserved sequences in the final intron of MDM2 are essential for the regulation of alternative splicing of MDM2 in response to stress [J]. Exp Cell Res,2009,315(19):3419-3432
33. Pros E, Femandez-Rodriguez J, Canet B, et al. Antisense therapeutics for neurofibromatosis type 1 caused by deep intronic mutations [J]. Hum Mutat,2009. 30(3):454-462
34. Holla L, Nakken S, Mattingsdal M, et al. Effects of intronic mutations in the LDLR gene on pre-mRNA splicing:Comparison of wet-lab and bioinformatics analyses [J]. Mol Genet Metab,2009,96(4):245-252
35. Yao Y, Schroder J, Nellaker C, et al. Elevated levels of human endogenous retrovirus-W transcripts in blood cells from patients with first episode schizophrenia [J].Genes Brain Behav,2008,7(1):103-112
36. Habara Y, Takeshima Y, Awano H, et al. In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by+1G-->A mutations in introns of the dystrophin gene [J]. J Med Genet,2009,46(8):542-547
37. Olsson A, Lind L, Thornell LE, et al. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect [J]. Hum Mol Genet,2008; 17(11):1666-1672
38. Xiao S, Tjostheim S, Sanelli T, et al. An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology [J]. J Neurosci,2008,28(8):1833-1840