小激活RNA在肿瘤中的研究进展
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摘要
RNA激活(RNA activation,RNAa)是由小激活RNA(smallactivatingRNA,saRNA)介导的基因上调表达机制。目前,RNAa的研究主要集中在肿瘤领域。RNAa介导的基因激活在肿瘤的发生机制研究和治疗方面具有优势。saRNA通过特异性上调抑癌基因的表达水平,抑制肿瘤细胞的增殖、侵袭和转移等生物学行为,从而在基因水平实现治疗肿瘤的目的。本文总结了近年来saRNA介导的RNAa在肿瘤治疗中的研究进展,并进一步分析其临床应用前景。
RNA activation(RNAa) is gene expression up-regulation mediated by small activating RNA(saRNA). At present, the research of RNAa mainly focuses on the tumors. The gene activation mediated by RNAa has obvious advantages in the research and treatment of tumors. By up-regulating the expression of tumor suppressor gene, saRNA can inhibit the malignant biological behaviors of tumor cells, such as proliferation, invasion and metastasis, so as to achieve the therapeutic effects at the gene level. This article summarizes the recent reports on RNAa mediated by saRNA in the treatment of tumors, and also analyzes the clinical application prospects of saRNA.
RNA activation(RNAa) is gene expression up-regulation mediated by small activating RNA(saRNA). At present, the research of RNAa mainly focuses on the tumors. The gene activation mediated by RNAa has obvious advantages in the research and treatment of tumors. By up-regulating the expression of tumor suppressor gene, saRNA can inhibit the malignant biological behaviors of tumor cells, such as proliferation, invasion and metastasis, so as to achieve the therapeutic effects at the gene level. This article summarizes the recent reports on RNAa mediated by saRNA in the treatment of tumors, and also analyzes the clinical application prospects of saRNA.
引文
[7] LI LC, OKINO ST, ZHAO H, et al.Small dsRNAs induce transcriptional activation in human cells[J].Proc Natl Acad Sci U S A, 2006,103(46):17337-1 7342.
[2] JANOWSKI BA, YOUNGER ST, HARDY DB,et al. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs[J]. Nat Chem Biol, 2007,3(3):166-173.
[3] PORTNOY V, HUANG V, PLACE RF,et al. Small RNA and transcriptional upregulation[J]. Wiley Interdiscip Rev RNA, 2011,2(5):748-760.
[4] WANG LL, GUO HH, ZHAN Y, et al.Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth[J]. Oncotarget,2017, 8(15):25055-25065.
[5] HUANG V, QIN Y, WANG J, et al. RNAa is conserved in mammalian cells[J].PLoS One, 2010, 5(1):e8848.
[6] REEBYE V, HUANG KW, LIN V, et al.Gene activation of CEBPA using saRNA:preclinical studies of the first in human saRNA drug candidate for liver cancer[J].Oncogene, 2018, 37(24):3216-3228.
[7] LI C, JIANG W, HU Q, et al. Enhancing DPYSL 3 gene expression via a promoter-targeted small activating RNA approach suppresses cancer cell motility and metastasis[J]. Oncotarget,2016, 7(16):22893-22910.
[8]王国玉,夏伟,倪晶,等. saRNA调控NIS基因介导131I对肝癌HepG2细胞体外抑制作用的实验研究[J].标记免疫分析与临床,201 5, 22(11):1138-1143.
[9]陈金飚,颜醒愚.saRNA上调人前列腺癌PC-3细胞中Numb基因表达的研究[J].重庆医学,201 6, 45(4):439-441.
[10] XIE D, SHANG L, PENG L, et al. Upregulation of VEZT by small activating RNA inhibits the proliferation, invasion and migration of gastric cancer cells[J].Biochem Biophys Res Commun, 2017,482(4):542-548.
[11] YANG K, ZHENG XY, QIN J, et al. Upregulation of p21WAF1/Cip1 by saRNA induces G1-phase arrest and apoptosis in T24 human bladder cancer cells[J].Cancer Lett, 2008, 265(2):206-214.
[12] KANG MR, YANG G, PLACE RF, et al.Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth[J]. Cancer Res, 201 2,72(19):5069-5079.
[13]庄菊花,夏伟,倪晶,等.saRNA调控p21基因表达对肝癌细胞的抑制作用[J].临床和实验医学杂志,2016,1 5(10):929-933.
[14]杨哲,朱勇,赵瑞.靶向p21基因saRNA抑制肝癌细胞生长实验研究[J].中华实用诊断与治疗杂志,2015,29(2):132-135.
[15] KOSAKA M, KANG MR, YANG G, et al.Targeted p21WAF1/CIP1 activation by RNAa inhibits hepatocellular carcinoma cells[J].Nucleic Acid Ther, 2012, 22(5):335-343.
[16]吴嘉,陈忠,杨为民,等.p53表达下调对saRNA介导p21基因激活的影响研究[J].现代泌尿生殖肿瘤杂志,2015,7(6):350-353.
[17] MARCEL V, NGUYEN VAN LONG F,DIAZ JJ. 40 Years of research put p53in translation[J]. Cancers, 2018, 10(5):E152.
[18]张腾,袁梅,俞同福.肿瘤中TP53诱导的糖酵解和凋亡调节因子及其靶向治疗研究进展[J].肿瘤,2016,36(12):1383-1388.
[19]刘健,李春晓,雷箴,等.结直肠癌中p53对组蛋白去乙酰化酶2表达的调控作用[J].肿瘤,2017, 37(10):1017-1023.
[20] WANG C, GE Q, ZHANG Q, et al.Targeted p53 activation by saRNA suppresses human bladder cancer cells growth and metastasis[J]. J Exp Clin Cancer Res, 2016, 35:53.
[21] GE Q,WANG C,RUAN Y, et al.Overexpression of p53 activated by small activating RNA suppresses the growth of human prostate cancer cells[J]. Onco Targets Ther, 2016,9:231-241.
[22]李述,贺勇,曾兴,等.SASH1-IQGAP1-E-cadherin信号轴可能调节乳腺癌转移[J].肿瘤,201 7, 37(6):633-641.
[23] JUNXIA W, PING G, YUAN H, et al. Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo[J].Cancer Sci, 2010,101(8):1790-1796.
[24] BAJRAMI I, MARLOW R, VAN DE VEN M, et al.E-Cadherin/ROS1 inhibitor synthetic lethality in breast cancer[J]. Cancer Discov, 2018, 8(4):498-515.
[25] WU Z, LI Y, LI Z, et al. Transcriptional regulation of E-cadherin by small activating RNA:A new doublestranded RNA[J]. Int J Oncol, 2016,49(4):1620-1628.
[26] MAO Q, LI Y, ZHENG X, et al. Upregulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells[J]. Biochem Biophys Res Commun, 2008, 375(4):566-570.
[27] MAO Q, ZHENG X, YANG K, et al.Suppression of migration and invasion of PC3 prostate cancer cell line via activating E-cadherin expression by small activating RNA[J]. Cancer Invest,2010, 28(1 0):1013-1018.
[28] VOUTILA J, REEBYE V, ROBERTS TC, et al.Development and mechanism of small activating RNA targeting CEBPA, a novel therapeutic in clinical trials for liver cancer[J].Mol Ther, 201 7, 25(12):2705-2714.
[29] YOON S, HUANG KW, REEBYE V,et al. Targeted delivery of C/EBP alpha-saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo[J]. Mol Ther, 2016,24(6):1106-1 116.
[30] GAGNON KT, LI L, CHU YJ, et al. RNAi factors are present and active in human cell nuclei[J]. Cell Rep, 2014,6(1):211-221.
[31] WANG T, LI M, YUAN H, et al. saRNA guided iNOS up-regulation improves erectile function of diabetic rats[J].J Urol, 2013, 190(2):790-798.
[32]袁慧星,周炳炎,矫阳田,等.腺病毒介导的小激活RNA基因治疗对老龄大鼠阴茎勃起功能的改善[J].华中科技大学学报(医学版),201 7,46(5):511-5148.
[33]王运,黄文华,孙军.小激活RNA(saRNA):肿瘤治疗新途径[J].中国生物化学与分子生物学报,2014,30(10):979-984.
[34]孙雨沛,胡火军,李格,等.小激活RN A(saRNA)与恶性肿瘤的研究进展[J].肿瘤防治研究,2018,45(1):52-55.
[2] JANOWSKI BA, YOUNGER ST, HARDY DB,et al. Activating gene expression in mammalian cells with promoter-targeted duplex RNAs[J]. Nat Chem Biol, 2007,3(3):166-173.
[3] PORTNOY V, HUANG V, PLACE RF,et al. Small RNA and transcriptional upregulation[J]. Wiley Interdiscip Rev RNA, 2011,2(5):748-760.
[4] WANG LL, GUO HH, ZHAN Y, et al.Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth[J]. Oncotarget,2017, 8(15):25055-25065.
[5] HUANG V, QIN Y, WANG J, et al. RNAa is conserved in mammalian cells[J].PLoS One, 2010, 5(1):e8848.
[6] REEBYE V, HUANG KW, LIN V, et al.Gene activation of CEBPA using saRNA:preclinical studies of the first in human saRNA drug candidate for liver cancer[J].Oncogene, 2018, 37(24):3216-3228.
[7] LI C, JIANG W, HU Q, et al. Enhancing DPYSL 3 gene expression via a promoter-targeted small activating RNA approach suppresses cancer cell motility and metastasis[J]. Oncotarget,2016, 7(16):22893-22910.
[8]王国玉,夏伟,倪晶,等. saRNA调控NIS基因介导131I对肝癌HepG2细胞体外抑制作用的实验研究[J].标记免疫分析与临床,201 5, 22(11):1138-1143.
[9]陈金飚,颜醒愚.saRNA上调人前列腺癌PC-3细胞中Numb基因表达的研究[J].重庆医学,201 6, 45(4):439-441.
[10] XIE D, SHANG L, PENG L, et al. Upregulation of VEZT by small activating RNA inhibits the proliferation, invasion and migration of gastric cancer cells[J].Biochem Biophys Res Commun, 2017,482(4):542-548.
[11] YANG K, ZHENG XY, QIN J, et al. Upregulation of p21WAF1/Cip1 by saRNA induces G1-phase arrest and apoptosis in T24 human bladder cancer cells[J].Cancer Lett, 2008, 265(2):206-214.
[12] KANG MR, YANG G, PLACE RF, et al.Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth[J]. Cancer Res, 201 2,72(19):5069-5079.
[13]庄菊花,夏伟,倪晶,等.saRNA调控p21基因表达对肝癌细胞的抑制作用[J].临床和实验医学杂志,2016,1 5(10):929-933.
[14]杨哲,朱勇,赵瑞.靶向p21基因saRNA抑制肝癌细胞生长实验研究[J].中华实用诊断与治疗杂志,2015,29(2):132-135.
[15] KOSAKA M, KANG MR, YANG G, et al.Targeted p21WAF1/CIP1 activation by RNAa inhibits hepatocellular carcinoma cells[J].Nucleic Acid Ther, 2012, 22(5):335-343.
[16]吴嘉,陈忠,杨为民,等.p53表达下调对saRNA介导p21基因激活的影响研究[J].现代泌尿生殖肿瘤杂志,2015,7(6):350-353.
[17] MARCEL V, NGUYEN VAN LONG F,DIAZ JJ. 40 Years of research put p53in translation[J]. Cancers, 2018, 10(5):E152.
[18]张腾,袁梅,俞同福.肿瘤中TP53诱导的糖酵解和凋亡调节因子及其靶向治疗研究进展[J].肿瘤,2016,36(12):1383-1388.
[19]刘健,李春晓,雷箴,等.结直肠癌中p53对组蛋白去乙酰化酶2表达的调控作用[J].肿瘤,2017, 37(10):1017-1023.
[20] WANG C, GE Q, ZHANG Q, et al.Targeted p53 activation by saRNA suppresses human bladder cancer cells growth and metastasis[J]. J Exp Clin Cancer Res, 2016, 35:53.
[21] GE Q,WANG C,RUAN Y, et al.Overexpression of p53 activated by small activating RNA suppresses the growth of human prostate cancer cells[J]. Onco Targets Ther, 2016,9:231-241.
[22]李述,贺勇,曾兴,等.SASH1-IQGAP1-E-cadherin信号轴可能调节乳腺癌转移[J].肿瘤,201 7, 37(6):633-641.
[23] JUNXIA W, PING G, YUAN H, et al. Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo[J].Cancer Sci, 2010,101(8):1790-1796.
[24] BAJRAMI I, MARLOW R, VAN DE VEN M, et al.E-Cadherin/ROS1 inhibitor synthetic lethality in breast cancer[J]. Cancer Discov, 2018, 8(4):498-515.
[25] WU Z, LI Y, LI Z, et al. Transcriptional regulation of E-cadherin by small activating RNA:A new doublestranded RNA[J]. Int J Oncol, 2016,49(4):1620-1628.
[26] MAO Q, LI Y, ZHENG X, et al. Upregulation of E-cadherin by small activating RNA inhibits cell invasion and migration in 5637 human bladder cancer cells[J]. Biochem Biophys Res Commun, 2008, 375(4):566-570.
[27] MAO Q, ZHENG X, YANG K, et al.Suppression of migration and invasion of PC3 prostate cancer cell line via activating E-cadherin expression by small activating RNA[J]. Cancer Invest,2010, 28(1 0):1013-1018.
[28] VOUTILA J, REEBYE V, ROBERTS TC, et al.Development and mechanism of small activating RNA targeting CEBPA, a novel therapeutic in clinical trials for liver cancer[J].Mol Ther, 201 7, 25(12):2705-2714.
[29] YOON S, HUANG KW, REEBYE V,et al. Targeted delivery of C/EBP alpha-saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo[J]. Mol Ther, 2016,24(6):1106-1 116.
[30] GAGNON KT, LI L, CHU YJ, et al. RNAi factors are present and active in human cell nuclei[J]. Cell Rep, 2014,6(1):211-221.
[31] WANG T, LI M, YUAN H, et al. saRNA guided iNOS up-regulation improves erectile function of diabetic rats[J].J Urol, 2013, 190(2):790-798.
[32]袁慧星,周炳炎,矫阳田,等.腺病毒介导的小激活RNA基因治疗对老龄大鼠阴茎勃起功能的改善[J].华中科技大学学报(医学版),201 7,46(5):511-5148.
[33]王运,黄文华,孙军.小激活RNA(saRNA):肿瘤治疗新途径[J].中国生物化学与分子生物学报,2014,30(10):979-984.
[34]孙雨沛,胡火军,李格,等.小激活RN A(saRNA)与恶性肿瘤的研究进展[J].肿瘤防治研究,2018,45(1):52-55.