miR-203 Suppresses the Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting Oncogene ADAM9 and Oncogenic Long Non-coding RNA HULC
miR-203 Suppresses the Proliferation and Metastasis of Hepatocellular Carcinoma by Targeting Oncogene ADAM9 and Oncogenic Long Non-coding RNA HULC
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DOI：
10.2174/1871520615666150716105955
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发表时间：
2016-01-01
影响因子：
2.8
通讯作者：
Peng, Baogang
中科院分区：
文献类型：
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作者：
Wan, Daiwei;Shen, Shunli;Peng, Baogang
MicroRNAs （miRNAs）通过在转录后水平调控基因被整合到致瘤程序中。长链非编码rna （lncrna）是mirna的新靶标。在这里，我们报道了miR-203下调与肝细胞癌患者的晚期临床特征和较差的总生存期（OS）密切相关。我们还证实，miR-203和癌基因ADAM9（一种崩解素和金属蛋白酶9）/致癌长链非编码RNA HULC（在肝癌中高度上调）在肝细胞癌（HCC）组织或细胞系中呈负表达。更有趣的是，上调miR-203可降低HCC癌细胞中ADAM9和HULC的表达。过表达miR-203可明显抑制细胞增殖、侵袭并诱导细胞凋亡。此外，我们发现miR-203通过一种新的转录后调控机制调节ADAM9和HULC。过表达的HULC部分恢复了mir -203介导的抗肿瘤作用。这些结果表明miR-203通过下调ADAM9和HULC发挥抑瘤作用，在癌症治疗中具有潜在的应用前景。
MicroRNAs (miRNAs) have been integrated into tumorigenic programs by regulating genes at post-transcriptional level. Long non-coding RNAs (lncRNAs) are novel targets for miRNAs. Here, we reported that miR-203 down-regulation was closely linked to advanced clinical features and poor overall survival (OS) of patients with hepatocellular carcinoma. We also confirmed that miR-203 and oncogene ADAM9 (a disintegrin and metalloproteinase 9)/oncogenic long non-coding RNA HULC (highly up-regulated in liver cancer) were inversely expressed in hepatocellular carcinoma (HCC) tissues or cell lines. More intriguingly, up-regulation of miR-203 diminished the expression of ADAM9 and HULC in HCC cancer cells. Over-expression of miR-203 could markedly inhibit cell proliferation, invasion and induce cell apoptosis. Furthermore, we identified that miR-203 modulated ADAM9 and HULC in a novel post-transcriptional regulatory mechanism. Over-expression of HULC partly rescued the miR-203-mediated antitumor effects. These results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment.