MicroRNA-495 suppresses cell proliferation and invasion of hepatocellular carcinoma by directly targeting insulin-like growth factor receptor-1 (Retracted article. See vol. 24, 2022)
MicroRNA-495 suppresses cell proliferation and invasion of hepatocellular carcinoma by directly targeting insulin-like growth factor receptor-1 (Retracted article. See vol. 24, 2022)
复制标题
MicroRNA-495通过直接靶向胰岛素样生长因子受体抑制肝细胞癌的细胞增殖和侵袭1
DOI：
10.3892/etm.2017.5467
复制
发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Xia, Wei
中科院分区：
文献类型：
--
作者：
Ye, Ying;Zhuang, Juhua;Xia, Wei
肝细胞癌（HCC）是世界范围内第五大常见恶性肿瘤和第二大常见癌症相关死亡原因。近年来，越来越多的研究报道microRNAs（miRNAs/miRs）在多种人类肿瘤中异常表达，并可能参与肝癌的发生和发展。基于miRNA的靶向治疗对不同的分子靶标有效，并且可以将癌细胞对治疗的敏感性提高数倍。因此，进一步验证参与HCC起始和进展的潜在重要miRNAs可能为HCC患者的治疗提供有价值的见解。miR-495在多种类型的人类癌症中异常表达。然而，miR-495在HCC中的表达水平和作用尚未完全阐明。在本研究中，miR-495在HCC组织和细胞系中表达频繁下调，并且miR-495表达水平与HCC患者的肿瘤大小、肿瘤淋巴结转移（TNM）分期和淋巴结转移显著相关。功能分析显示miR-495过表达抑制HCC细胞增殖和侵袭。胰岛素样生长因子受体-1（IGF 1 R）被确定为HCC中miR-495的直接靶基因。IGF 1 R在HCC组织中表达上调，且与miR-495表达水平呈负相关。IGF 1 R的上调挽救了miR-495诱导的HCC细胞增殖和侵袭中的肿瘤抑制作用，并且恢复的miR-495表达使HCC中的蛋白激酶B和细胞外调节的蛋白激酶信号通路失活。这些结果为HCC进展的分子机制提供了新的见解，并表明miR-495可作为该疾病患者的新治疗靶点进行研究。
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and second-most frequent cause of cancer-associated deaths worldwide. Previously, increasing studies report that microRNAs (miRNAs/miRs) are abnormally expressed in various types of human cancers and may participate in the tumourigenesis and tumour development of HCC. miRNA-based targeted therapy is effective against different molecular targets and may increase the sensitisation of cancer cells to therapy by several folds. Therefore, further validation of potentially important miRNAs involved in HCC initiation and progression may provide valuable insights into the treatment of patients with HCC. miR-495 is abnormally expressed in multiple types of human cancers. However, the expression level and roles of miR-495 in HCC have yet to be completely elucidated. In the present study, miR-495 expression was frequently downregulated in HCC tissues and cell lines, and miR-495 expression levels were significantly correlated with tumour size, tumor-node-metastasis (TNM) stage and lymph node metastasis in patients with HCC. Functional assays revealed that miR-495 overexpression inhibited cell proliferation and invasion in HCC. Insulin-like growth factor receptor-1 (IGF1R) was identified as a direct target gene of miR-495 in HCC. IGF1R was upregulated in HCC tissues and negatively correlated with miR-495 expression level. The upregulation of IGF1R rescued the miR-495-induced tumour-suppressive roles in HCC cell proliferation and invasion, and the restored miR-495 expression inactivated the protein kinase B and extracellular regulated protein kinase signalling pathways in HCC. These results provide novel insights into the molecular mechanism underlying HCC progression, and suggest that miR-495 may be investigated as a novel therapeutic target for patients with this disease.