Ye Ying, Zhuang Juhua, Wang Guangdong, He Saifei, Zhang Suiliang, Wang Guoyu, Ni Jing, Wang Jiening, Xia Wei
Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Department of Research and Development, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Exp Ther Med. 2018 Jan;15(1):1150-1158. doi: 10.3892/etm.2017.5467. Epub 2017 Nov 8.
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.
肝细胞癌（HCC）是全球第五大常见恶性肿瘤，也是癌症相关死亡的第二大常见原因。此前，越来越多的研究报道，微小RNA（miRNA/miR）在各种类型的人类癌症中异常表达，可能参与HCC的肿瘤发生和肿瘤发展。基于miRNA的靶向治疗对不同的分子靶点有效，可使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miRNA，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表达在HCC组织和细胞系中经常下调，且miR-495表达水平与HCC患者的肿瘤大小、肿瘤-淋巴结-转移（TNM）分期及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（IGF1R）被确定为HCC中miR-495的直接靶基因。IGF1R在HCC组织中上调，且与miR-495表达水平呈负相关。IGF1R的上调挽救了miR-495诱导的对HCC细胞增殖和侵袭的肿瘤抑制作用，而恢复miR-495表达使HCC中的蛋白激酶B和细胞外调节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可能作为该疾病患者的新型治疗靶点进行研究。
