miR-145 suppresses cell invasion in hepatocellular carcinoma cells: miR-145 targets ADAM17
miR-145 suppresses cell invasion in hepatocellular carcinoma cells: miR-145 targets ADAM17
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miR-145抑制肝细胞癌细胞的细胞侵袭：miR-145靶向ADAM17
DOI：
10.1111/hepr.12152
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发表时间：
2014-05-01
影响因子：
4.2
通讯作者：
Wang, Qian
中科院分区：
文献类型：
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作者：
Yang, Xue-wei;Zhang, Long-juan;Wang, Qian
AimmiR-145是一种候选肿瘤抑制miRNA。然而，miR-145是否参与肝细胞癌（HCC）的侵袭尚不清楚。因此，我们旨在探讨miR-145在控制HCC细胞侵袭中的作用和机制。方法转染pre-miR-145或anti-miR-145后，采用transwell法观察细胞的侵袭情况。荧光素酶报告试验用于确定分解素和金属蛋白酶17 （ADAM17）是否是miR-145的靶标。实时聚合酶链反应法检测miR-145和ADAM17 mRNA水平，western blot法检测ADAM17蛋白水平。采用Pearson相关检验评估20例HCC组织样本中ADAM17 mRNA表达与miR-145表达的相关性。结果smir -145在HCC组织和细胞系中显著下调。miR-145表达的缺失与肿瘤淋巴结转移分期、血管侵袭和肝内转移有关。过表达miR-145能够抑制肿瘤MHCC-97H细胞的侵袭，而敲低miR-145表达则诱导SMMC-7721细胞的侵袭。我们证明miR-145直接结合到ADAM17的3 '-非翻译区并抑制ADAM17的表达。在SMMC-7721细胞中敲低ADAM17可以部分逆转anti-miR-145的作用。在20个HCC组织标本中，miR-145的表达与ADAM17的表达呈负相关。结论miR-145可通过调节ADAM17的表达抑制HCC细胞侵袭。
AimmiR-145 is a candidate tumor suppressor miRNA. However, it is unknown whether miR-145 is involved in the invasion of hepatocellular carcinoma (HCC). Therefore, we aimed to explore the effect and mechanism of miR-145 in the control of HCC cell invasion.MethodsHCC cell invasion was evaluated by transwell assays after transfection with pre-miR-145 or anti-miR-145. A luciferase reporter assay was used to determine whether a disintegrin and metalloprotease 17 (ADAM17) were a target of miR-145. The levels of miR-145 and ADAM17 mRNA were detected by a real-time polymerase chain reaction assay, and the level of ADAM17 protein was measured by western blot analysis. Pearson's correlation test was used to assess the correlation between ADAM17 mRNA expression and miR-145 expression in 20 HCC tissue samples.ResultsmiR-145 was significantly downregulated in HCC tissues and cell lines. The loss of miR-145 expression was associated with the tumor-node-metastasis stage, vascular invasion and intrahepatic metastasis. The overexpression of miR-145 was able to suppress tumor MHCC-97H cell invasion, whereas the knockdown of miR-145 expression induced SMMC-7721 cell invasion. We demonstrated that miR-145 bound directly to the 3 '-untranslated region of ADAM17 and inhibited the expression of ADAM17. The knockdown of ADAM17 in SMMC-7721 cells could partially reverse the effects of anti-miR-145. miR-145 expression was inversely associated with ADAM17 expression in 20 HCC tissue specimens.ConclusionOur findings indicate that miR-145 could inhibit HCC cell invasion by regulating the expression of ADAM17.