Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells, miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5.
Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells, miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5.
复制标题
DOI：
10.18632/oncotarget.5642
复制
发表时间：
2015-11-10
期刊：
影响因子：
--
通讯作者：
Tang H
中科院分区：
文献类型：
--
作者：
Cao Y;Chen J;Wang D;Peng H;Tan X;Xiong D;Huang A;Tang H
B型肝炎病毒（HBV）是肝细胞癌（HCC）发生发展的主要危险因素。已有研究表明，病毒感染可干扰细胞microRNA（miRNA）的表达，参与致瘤性的发病过程。我们的miRNAs阵列数据表明miR-331- 3 p在HCC细胞系中表达增加，但miR-331- 3 p表达与HBV活性之间的关系尚不清楚。在此，我们观察到miR-331- 3 p在表达HBV的不同HCC细胞系中的表达升高。HBV，特别是HBx，通过增强其启动子活性促进miR-331- 3 p表达。利用miRNA靶点预测数据库miRBase，我们确定ING 5为miR-331- 3 p的新靶基因。miR-331- 3 p可通过直接靶向ING 5的3′-非翻译区（3′-UTR）来抑制ING 5的表达。如预测的那样，证实HBV通过促进miR-331- 3 p表达在mRNA和蛋白水平上抑制ING 5。我们的结果表明miR-331- 3 p表达通过抑制ING 5促进SMMC 7721细胞的增殖。ING 5过表达可促进肝癌细胞凋亡。我们还发现ING 5在HBV感染的HCC患者的肿瘤组织中的表达与其在癌旁组织中的表达相比降低。结论：HBV可上调miR-331- 3 p的表达，并通过抑制ING 5的表达促进肝癌细胞的增殖。这些数据为理解HBV相关的HCC发病机制提供了新的见解。
Hepatitis B virus (HBV) is a major risk factor for development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Our miRNAs array data indicated that miR-331-3p expression in HCC cell lines increased, but the relationship between miR-331-3p expression and HBV activity is unclear. Here, we observed elevated expression of miR-331-3p in different HCC cell lines expressing HBV. HBV, especially HBx, promotes miR-331-3p expression by enhancing its promoter activity. Using a miRNA target prediction database miRBase, we identified ING5 to be a novel target gene of miR-331-3p. miR-331-3p could inhibit ING5 expression by directly targeting its 3′-untranslated region (3′-UTR). As predicted, HBV was confirmed to repress ING5 at both mRNA and protein levels by promoting miR-331-3p expression. Our result indicated that miR-331-3p expression promotes proliferation of SMMC7721 cells by inhibiting ING5. ING5 overexpression promoted cell apoptosis in HCC cell lines. We also found ING5 expression was decreased in tumor tissue of HCC patient with HBV infection compared to its expression in para-carcinoma tissues. Conclusion: These results showed that miR-331-3p is upregulated by HBV and promotes proliferation of HCC cells though repression of ING5 expression. These data provide new insights for understanding the mechanisms of HBV-related HCC pathogenesis.