中国普外基础与临床杂志

中国普外基础与临床杂志

miR-106a-5p在胃癌细胞和胃癌组织中的表达及其调控靶基因信号通路富集分析

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目的 检测 miR-106a-5p 在胃癌细胞和胃癌组织中的表达并分析其表达与胃癌患者临床病理特征的关系,并采用生物信息学方法分析其靶基因和富集的信号通路。 方法 采用实时荧光定量 PCR 法检测 miR-106a-5p 在正常胃黏膜上皮细胞 GES-1 和不同分化程度的胃癌细胞 AGS(高分化)、MKN-28(中分化)、HGC-27(未分化)、MGC-803(低分化)、BGC-823(低分化)、MKN-45(中分化)及 SGC-7901(中分化)和组织(58 例胃癌组织及其相应的距离癌灶 5 cm 以上且经 HE 染色证实均无癌细胞的癌周组织)中的表达,采用 mirWALK 网站数据库的预测软件预测其靶基因并选择 3 个以上软件支持的靶基因,运用 DAVID 6.7 软件在线富集选择的靶基因参与的信号通路。 结果 与正常胃黏膜上皮细胞 GES-1 比较,miR-106a-5p 在不同分化程度的胃癌细胞 AGS、SGC-7901、MKN-45、MGC-803、BCG-823、HGC-27 中的表达量明显上调(P<0.01 或P<0.001),而在 MKN-28 细胞中未见上调(P>0.05)。与相应的癌旁组织比较,mir-106a-5p 在胃癌组织中的表达量在 36 例中表达上调(即高表达),在 18 例中表达下调(即低表达),4 例在变化不明显。miR-106a-5p 在胃癌组织中表达与淋巴结转移(P=0.003)和侵犯深度有关(P=0.034),而与胃癌患者的年龄、性别、组织学分化程度、TNM 分期、淋巴管侵犯、血管侵犯及 Borrmann 分型无关(P>0.05)。生物信息学分析提示,miR-106a-5p 的靶基因富集存在于与肿瘤相关的 32 个信号通路中。 结论 miR-106a-5p 在胃癌细胞系及胃癌组织中高表达并与淋巴结转移以及浸润深度有关,其有可能作为一具备潜在研究价值的癌基因。

Objective To detect expression of miR-106a-5p in gastric cancer cells and gastric cancer tissue and analyze relationship of it’s expression with clinicopathologic characteristics of patient with gastric cancer, and analyze target genes with enriched pathway using bioinformatics method. Methods The expressions of mir-106a-5p in the different differentiation gastric cancer cells HGC-27, MGC-803, BGC-823, MKN-45, SGC-7901, the normal gastric mucosal epithelial cells GES-1, and the gastric cancer tissue and the corresponding adjacent tissue were detected by the real-time fluorescent quantitative PCR. Furthermore, the target genes of miR-106a-5p were predicted by using more than three softwares affiliated to mirWALK web database and the signal pathways of target genes were enriched by DAVID 6.7 software. Results The expression of mir-106a-5p in the different degree of differentiation of gastric cancer cells compared with normal gastric mucosa cell line were up-regulated except MKN-45 cell line, and the expression of mir-106a-5p in gastric cancer tissues compared with adjacent tissues was also up-regulated, the expression of mir-106a-5p in gastric cancer were associated with lymph node metastasis and invasion depth. Bioinformatics analysis showed that the target gene of mir-106a-5p were enriched in multiple signaling pathways associated with cancer. Conclusion miR-106a-5p is a molecular marker of high expression in gastric cancer and a potential cancer gene associated with lymph node metastasis and invasion depth.

关键词: miR-106a-5p; 胃癌; 肿瘤分子标志物

Key words: miR-106a-5p; gastric cancer; tumor molecular marker

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1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. 杜亚琼, 姜波健, 俞继卫. miRNA在胃癌发生发展中的作用. 中国普外基础与临床杂志, 2016, 23(4): 499-502.
3. Li X, Zhou Q, Tao L, et al. MicroRNA-106a promotes cell migration and invasion by targeting tissue inhibitor of matrix metalloproteinase 2 in cervical cancer. Oncol Rep, 2017, 38(3): 1774-1782.
4. Chen L, Zhang F, Sheng XG, et al. MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells. Oncol Rep, 2016, 36(4): 2135-2141.
5. 李金虎, 赵晓俊, 张江磊, 等. miR-106a在人前列腺癌中的临床意义及生物学机制研究. 中国免疫学杂志, 2015, 31(7): 955-959.
6. Xie X, Liu HT, Mei J, et al. miR-106a promotes growth and metastasis of non-small cell lung cancer by targeting PTEN. Int J Clin Exp Pathol, 2015, 8(4): 3827-3834.
7. Ma HL, Wen XP, Zhang XZ, et al. miR-106a* inhibits the proliferation of esophageal carcinoma cells by targeting CDK2-associated Cullin 1 (CACUL1). Cell Mol Biol (Noisy-le-grand), 2015, 61(4): 56-62.
8. Hao H, Xia G, Wang C, et al. miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7. Med Mol Morphol, 2017, 50(2): 76-85.
9. Manne RK, Agrawal Y, Bargale A, et al. A MicroRNA/Ubiquitin ligase feedback loop regulates slug-mediated invasion in breast cancer. Neoplasia, 2017, 19(6): 483-495.
10. Li D, Wang Z, Chen Z, et al. MicroRNA-106a-5p facilitates human glioblastoma cell proliferation and invasion by targeting adenomatosis polyposis coli protein. Biochem Biophys Res Commun, 2016, 481(3-4): 245-250.
11. Zhu M, Zhang N, He S, et al. MicroRNA-106a targets TIMP2 to regulate invasion and metastasis of gastric cancer. FEBS Lett, 2014, 588(4): 600-607.
12. Sierzega M, Kaczor M, Kolodziejczyk P, et al. Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331. Br J Cancer, 2017, 117(2): 266-273.
13. Zhu M, Zhang N, He S, et al. MicroRNA-106a functions as an oncogene in human gastric cancer and contributes to proliferation and metastasis in vitro and in vivo. Clin Exp Metastasis, 2016, 33(5): 509-519.
14. 李海龙, 宋耀辉, 陈兆峰, 等. miR-20a-5p/miR-20b-5p在胃癌细胞和组织中的表达及调控靶基因信号通路富集分析. 临床检验杂志, 2017, 35(11): 822-827.
15. 孔桂香, 黄晓俊, 金安琴, 等. 甘肃省河西地区33年胃镜检出胃癌的流行病学分析. 肿瘤防治研究, 2011, 38(12): 1438-1442.
16. Wang Z, Liu M, Zhu H, et al. miR-106a is frequently upregulated in gastric cancer and inhibits the extrinsic apoptotic pathway by targeting FAS. Mol Carcinog, 2013, 52(8): 634-646.
17. Pan YJ, Wei LL, Wu XJ, et al. MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5. Cell Death Dis, 2017, 8(10): e3155.
18. Luo B, Kang N, Chen Y, et al. Oncogene miR-106a promotes proliferation and metastasis of prostate cancer cells by directly targeting PTEN in vivo and in vitro. Minerva Med, 2018, 109(1): 24-30.
19. He QY, Wang GC, Zhang H, et al. miR-106a-5p suppresses the proliferation, migration, and invasion of osteosarcoma cells by targeting HMGA2. DNA Cell Biol, 2016, 35(9): 506-520.
20. Ma Y, Zhang H, He X, et al. miR-106a* inhibits the proliferation of renal carcinoma cells by targeting IRS-2. Tumour Biol, 2015, 36(11): 8389-8398.
21. Zhi F, Zhou G, Shao N, et al. miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and promotes apoptosis by targeting FASTK. PLoS One, 2013, 8(8): e72390.
22. Zhang Y, Lu Q, Cai X. MicroRNA-106a induces multidrug resistance in gastric cancer by targeting RUNX3. FEBS Lett, 2013, 587(18): 3069-3075.
23. Yang G, Zhang R, Chen X, et al. MiR-106a inhibits glioma cell growth by targeting E2F1 independent of p53 status. J Mol Med (Berl), 2011, 89(10): 1037-1050.
24. Zhou X, Zhu W, Li H, et al. Diagnostic value of a plasma microRNA signature in gastric cancer: a microRNA expression analysis. Sci Rep, 2015, 5: 11251.
25. Tsujiura M, Ichikawa D, Komatsu S, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer, 2010, 102(7): 1174-1179.
26. Wang JL, Hu Y, Kong X, et al. Candidate microRNA biomarkers in human gastric cancer: a systematic review and validation study. PLoS One, 2013, 8(9): e73683.