MicroRNA-145 suppresses hepatocellular carcinoma by targeting IRS1 and its downstream Akt signaling.

Accumulating evidences have proved that dysregulation of microRNAs (miRNAs) is involved in cancer initiation and progression. In this study, we showed that miRNA-145 level was significantly decreased in hepatocellular cancer (HCC) tissues and cell lines, and its low expression was inversely associated with the abundance of insulin receptor substrate 1 (IRS1), a key mediator in oncogenic insulin-like growth factor (IGF) signaling. We verified IRS1 as a direct target of miR-145 using Western blotting and luciferase reporter assay. Further, the restoration of miR-145 in HCC cell lines suppressed cancer cell growth, owing to down-regulated IRS1 expression and its downstream Akt/FOXO1 signaling. Our results demonstrated that miR-145 could inhibit HCC through targeting IRS1 and its downstream signaling, implicating the loss of miR-145 regulation may be a potential molecular mechanism causing aberrant oncogenic signaling in HCC.

Wang Y ，Hu C ，Cheng J ，Chen B ，Ke Q ，Lv Z ，Wu J ，Zhou Y ... -  《-》

MiR-145 modulates multiple components of the insulin-like growth factor pathway in hepatocellular carcinoma.

Law PT ，Ching AK ，Chan AW ，Wong QW ，Wong CK ，To KF ，Wong N ... -  《-》

MicroRNA-105 suppresses cell proliferation and inhibits PI3K/AKT signaling in human hepatocellular carcinoma.

A growing amount of evidence supports that microRNA (miRNA) dysregulation is involved in cancer progression by directly downregulating multiple targets. Elucidating the underlying mechanism of miRNA in carcinogenesis may improve diagnostic and therapeutic strategies for malignancy. In the current study, we found that miR-105 expression was markedly downregulated in both hepatocellular carcinoma (HCC) cell lines and clinical HCC tissues, compared with normal human hepatocyte and adjacent non-cancerous tissues, respectively. Ectopic miR-105 expression suppressed, whereas inhibiting miR-105 promoted the proliferation and tumorigenicity of HCC cells both in vitro and in vivo. Furthermore, we demonstrated that miR-105 could deactivated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway by downregulating insulin receptor substrate-1, 3-phosphoinositide-dependent protein kinase-1 and AKT1 directly, resulting in increasing cyclin-dependent kinase inhibitors 1A and 1B (p21(Cip1) and p27(Kip1)) and decreasing cyclin D1 expression in HCC. Therefore, our results suggest that miR-105 functions as a potential tumor suppressor by inhibiting the PI3K/AKT signaling pathway and might represent a potential therapeutic target for HCC patients.

Shen G ，Rong X ，Zhao J ，Yang X ，Li H ，Jiang H ，Zhou Q ，Ji T ，Huang S ，Zhang J ，Jia H ... -  《-》

MiR-384 regulated IRS1 expression and suppressed cell proliferation of human hepatocellular carcinoma.

Lai YY ，Shen F ，Cai WS ，Chen JW ，Feng JH ，Cao J ，Xiao HQ ，Zhu GH ，Xu B ... -  《-》

MicroRNA-1468 promotes tumor progression by activating PPAR-γ-mediated AKT signaling in human hepatocellular carcinoma.

Liu Z ，Wang Y ，Dou C ，Sun L ，Li Q ，Wang L ，Xu Q ，Yang W ，Liu Q ，Tu K ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》