MicroRNA-105 suppresses cell proliferation and inhibits PI3K/AKT signaling in human hepatocellular carcinoma
Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en inhibant la voie de signalisation PI3K/AKT, le micro-ARN miR-105 exerce une fonction de suppresseur de tumeurs dans le carcinome hépatocellulaire
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 to normal human hepatocyte and adjacent non-cancerous tissues, respectively. Ectopic miR-105 expression suppressed, while 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(IRS1), 3-phosphoinositide dependent protein kinase-1(PDK1) and AKT1 directly, resulting in increasing cyclin-dependent kinase inhibitors 1A and 1B (p21Cip1 and p27Kip1) 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.
http://carcin.oxfordjournals.org/content/early/2014/10/01/carcin.bgu208.abstract