胃癌组织中piR-9994的表达及其与PIWIL4表达的相关性
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摘要
目的探讨piR-9994在胃癌中的表达及其与临床病理特征的关系,并分析其与PIWIL4表达的相关性。方法采用qRT-PCR法检测76例胃癌及癌旁组织中piR-9994的表达,采用免疫组化En Vision法检测PIWIL4的表达,并复习相关文献。结果 piR-9994在胃癌组织中的表达比癌旁组织上调2. 3倍(P=0. 002 2)。Ⅲ+Ⅳ期胃癌组piR-9994的表达比Ⅰ+Ⅱ期胃癌组上调3. 5倍(P=0. 002),神经侵犯组比未侵犯组上升2. 5倍(P=0. 036)。PIWIL4在胃癌组织中的表达明显高于癌旁组织(χ2=18. 346,P <0. 001),其中Ⅲ+Ⅳ期胃癌组高于Ⅰ+Ⅱ期胃癌组(χ2=8. 60,P=0. 003)。胃癌组织中piR-9994的表达与PIWIL4表达呈正相关(r=0. 231,P <0. 05)。结论 piR-9994在胃癌组织中过表达并与肿瘤分期、神经侵犯密切相关,piR-9994可能通过调节PIWIL4表达促进胃癌的发生、发展,piR-9994有望成为判断胃癌恶性程度及预后的分子标志物。
Purpose To explore the relationship between the expression level of piR-9994 in gastric cancer and its clinical pathological features,and to analyze its correlation with PIWIL4 expression. Methods Express of piR-9994 and PIWIL4 in 76 cases of human gastric cancer tissue with different clinical stage and differentiated degree and matching adjacent tissue were detected by qRT-PCR and immunohistochemistry,respectively.Results The expression of piR-9994 in gastric cancer was 2. 3times higher than that in paracancerous tissues( P = 0. 002 2).The expression of piR-9994 in stage Ⅲ + Ⅳ gastric cancer was3. 5 times higher than that in stage Ⅰ + Ⅱ( P = 0. 002),and the expression of piR-9994 in cancers with nerve invasion was 2.5 times higher than that in cancers without invasion( P =0. 036). The positive expression of PIWIL4 in gastric cancer tissues was significantly higher than that in adjacent tissues( χ~2=18. 346,P < 0. 001),and the expression of PIWIL 4 in stageⅢ + Ⅳ gastric cancer group was higher than that stage Ⅰ + Ⅱgastric cancer group( χ2= 8. 60,P = 0. 003). There was a positive correlation between piR-9994 expression and PIWIL4 expression in gastric carcinoma( r = 0. 231,P < 0. 05). Conclusion piR-9994 overexpression in gastric cancer tissues is closely related to tumor staging and nerve invasion,and piR-9994 may pro-mote the occurrence and progression of gastric cancer by regulating PIWIL4 expression. piR-9994 may be a molecular markers for judging malignant degree and prognosis of gastric cancer.
Purpose To explore the relationship between the expression level of piR-9994 in gastric cancer and its clinical pathological features,and to analyze its correlation with PIWIL4 expression. Methods Express of piR-9994 and PIWIL4 in 76 cases of human gastric cancer tissue with different clinical stage and differentiated degree and matching adjacent tissue were detected by qRT-PCR and immunohistochemistry,respectively.Results The expression of piR-9994 in gastric cancer was 2. 3times higher than that in paracancerous tissues( P = 0. 002 2).The expression of piR-9994 in stage Ⅲ + Ⅳ gastric cancer was3. 5 times higher than that in stage Ⅰ + Ⅱ( P = 0. 002),and the expression of piR-9994 in cancers with nerve invasion was 2.5 times higher than that in cancers without invasion( P =0. 036). The positive expression of PIWIL4 in gastric cancer tissues was significantly higher than that in adjacent tissues( χ~2=18. 346,P < 0. 001),and the expression of PIWIL 4 in stageⅢ + Ⅳ gastric cancer group was higher than that stage Ⅰ + Ⅱgastric cancer group( χ2= 8. 60,P = 0. 003). There was a positive correlation between piR-9994 expression and PIWIL4 expression in gastric carcinoma( r = 0. 231,P < 0. 05). Conclusion piR-9994 overexpression in gastric cancer tissues is closely related to tumor staging and nerve invasion,and piR-9994 may pro-mote the occurrence and progression of gastric cancer by regulating PIWIL4 expression. piR-9994 may be a molecular markers for judging malignant degree and prognosis of gastric cancer.
引文
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[9] Aravin A A,Sachidanandam R,Bour'chis D,et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice[J]. Mol Cell,2008,31(6):785-799.
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[12] Fu A,Jacobs D I,Hoffman A E,et al. PIWI-interacting RNA021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome[J]. Carcinogenesis,2015,36(10):1094-1102.
[13] Lim S L,Ricciardelli C,Oehler M K,et al. Overexpression of piRNA pathway genes in epithelial ovarian cancer[J]. PLo S One,2014,9(6):e99687.
[14] Busch J,Ralla B,Jung M,et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas[J]. J Exp Clin Cancer Res,2015,34:61.
[15] Law P T,Qin H,Ching A K,et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma[J]. J Hepatol,2013,58(6):1165-1173.
[16] Yao J,Wang Y W,Fang B B,et al. piR-651 and its function in95-D lung cancer cells[J]. Biomed Rep,2016,4(5):546-550.
[17] Cheng J,Guo J M,Xiao B X,et al. piRNA,the new non-coding RNA,is aberrantly expressed in human cancer cells[J]. Clin Chim Acta,2011,412(17-18):1621-1625.
[18] Martinez V D,Enfield K S,Rowbotham D A,et al. An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence[J]. Gastric Cancer,2016,19(2):660-665.
[19] Gou L T,Dai P,Yang J H,et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis[J]. Cell Res,2015,25(2):266.
[20] Zhang P,Kang J Y,Gou L T,et al. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes[J]. Cell Res,2015,25(2):193-207.
[21] Wang X,Tong X,Gao H,et al. Silencing HIWI suppresses the growth,invasion and migration of glioma cells[J]. Int J Oncol,2014,45(6):2385-2392.
[22] Krishnan P,Ghosh S,Graham K,et al. Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer[J].Oncotarget,2016,7(25):37944-37956.
[23] Yin D T,Wang Q,Chen L,et al. Germline stem cell gene PIWIL2 mediates DNA repair through relaxation of chromatin[J].PLo S One,2011,6(11):e27154.
[24] Xie Y,Yang Y,Ji D,et al. Hiwi downregulation,mediated by shRNA,reduces the proliferation and migration of human hepatocellular carcinoma cells[J]. Mol Med Rep,2015,11(2):1455-1461.
[25] Wang Y,Liu Y,Shen X,et al. The PIWI protein acts as a predictive marker for human gastric cancer[J]. Int J Clin Exp Pathol,2012,5(4):315-325.
[2] Aravin A A,Hannon G J. Small RNA silencing pathways in germ and stem cells[J]. Cold Spring Harb Symp Quant Biol,2008,73:283-290.
[3] Sugimoto K,Kage H,Aki N,et al. The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus[J]. Biochem Biophys Res Commun,2007,359(3):497-502.
[4] Wang Z,Liu N,Shi S,et al. The role of PIWIL4,an argonaute family protein,in breast cancer[J]. J Biol Chem,2016,291(20):10646-10658.
[5] Li L,Yu C,Gao H,et al. Argonaute proteins:potential biomarkers for human colon cancer[J]. BMC Cancer,2010,10:38.
[6] Lin X,Hu D,Chen G,et al. Associations of THBS2 and THBS4polymorphisms to gastric cancer in a southeast Chinese population[J]. Cancer Genet,2016,209(5):215-222.
[7]刘东,陈云昭,李锋. microRNA在肿瘤表观遗传学中的研究进展[J].临床与实验病理学杂志,2010,26(6):742-746.
[8] Iwasaki Y W,Siomi M C,Siomi H. PIWI-Interacting RNA:its biogenesis and functions[J]. Annu Rev Biochem,2015,84:405-433.
[9] Aravin A A,Sachidanandam R,Bour'chis D,et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice[J]. Mol Cell,2008,31(6):785-799.
[10] Gunawardane L S,Saito K,Nishida K M,et al. A slicer-mediated mechanism for repeat-associated siRNA 5'end formation in Drosophila[J]. Science,2007,315(5818):1587-1590.
[11] Tan Y,Liu L,Liao M,et al. Emerging roles for PIWI proteins in cancer[J]. Acta Biochim Biophys Sin(Shanghai),2015,47(5):315-324.
[12] Fu A,Jacobs D I,Hoffman A E,et al. PIWI-interacting RNA021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome[J]. Carcinogenesis,2015,36(10):1094-1102.
[13] Lim S L,Ricciardelli C,Oehler M K,et al. Overexpression of piRNA pathway genes in epithelial ovarian cancer[J]. PLo S One,2014,9(6):e99687.
[14] Busch J,Ralla B,Jung M,et al. Piwi-interacting RNAs as novel prognostic markers in clear cell renal cell carcinomas[J]. J Exp Clin Cancer Res,2015,34:61.
[15] Law P T,Qin H,Ching A K,et al. Deep sequencing of small RNA transcriptome reveals novel non-coding RNAs in hepatocellular carcinoma[J]. J Hepatol,2013,58(6):1165-1173.
[16] Yao J,Wang Y W,Fang B B,et al. piR-651 and its function in95-D lung cancer cells[J]. Biomed Rep,2016,4(5):546-550.
[17] Cheng J,Guo J M,Xiao B X,et al. piRNA,the new non-coding RNA,is aberrantly expressed in human cancer cells[J]. Clin Chim Acta,2011,412(17-18):1621-1625.
[18] Martinez V D,Enfield K S,Rowbotham D A,et al. An atlas of gastric PIWI-interacting RNA transcriptomes and their utility for identifying signatures of gastric cancer recurrence[J]. Gastric Cancer,2016,19(2):660-665.
[19] Gou L T,Dai P,Yang J H,et al. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis[J]. Cell Res,2015,25(2):266.
[20] Zhang P,Kang J Y,Gou L T,et al. MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes[J]. Cell Res,2015,25(2):193-207.
[21] Wang X,Tong X,Gao H,et al. Silencing HIWI suppresses the growth,invasion and migration of glioma cells[J]. Int J Oncol,2014,45(6):2385-2392.
[22] Krishnan P,Ghosh S,Graham K,et al. Piwi-interacting RNAs and PIWI genes as novel prognostic markers for breast cancer[J].Oncotarget,2016,7(25):37944-37956.
[23] Yin D T,Wang Q,Chen L,et al. Germline stem cell gene PIWIL2 mediates DNA repair through relaxation of chromatin[J].PLo S One,2011,6(11):e27154.
[24] Xie Y,Yang Y,Ji D,et al. Hiwi downregulation,mediated by shRNA,reduces the proliferation and migration of human hepatocellular carcinoma cells[J]. Mol Med Rep,2015,11(2):1455-1461.
[25] Wang Y,Liu Y,Shen X,et al. The PIWI protein acts as a predictive marker for human gastric cancer[J]. Int J Clin Exp Pathol,2012,5(4):315-325.