miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Abstract

Abstract. microRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate gene expression. Increasing evidence has shown that the deregulation of miRNAs is linked to cancer. The overexpression of miR-224 has been reported in several human cancers. The aim of the present study was to investigate the function of miR-224 in the pathogenetic process of hepatocellular carcinoma (HCC), and the precise mechanism underlying its function. Both gain-of-function and loss-of function assays were conducted through transfection with miR-224 mimics and miR-224 inhibitors in the HepG2 liver carcinoma cell line. The data revealed that miR-224 exerts a significant role in promoting cell proliferation, migration and invasion. Western blot analysis showed that the phosphorylation levels of AKT positively correlated with endogenous levels of miR-224. In addition, results from a dual luciferase reporter assay showed that the expression of the serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A β isoform (PPP2R1B) is inhibited by miR-224; thus, it appears that PPP2R1B is a candidate target of miR-224 in HCC. These data suggest that miR-224 plays a significant role in HCC, possibly through the activation of the AKT signaling pathway by targeting PPP2R1B.

microRNA133a TargetsFoxl2and Promotes Differentiation of C2C12 into Myogenic Progenitor Cells

“…Not only are they involved in cell fate transitions, they also participate in numerous molecular signaling pathways and cellular processes (Ma et al, 2012;Jin et al, 2013). While transcription factors can transdifferentiate cells (Takahashi and Yamanaka, 2006;Huangfu et al, 2008;Kim et al, 2009), they must be introduced into the cell as DNA or highly modified mRNAs.…”

MicroRNA-224: as a potential target for miR-based therapy of cancer

“…The activation of PI3K/AKT/FOXO3a signaling restrains expression of p21Cip1 and p27Kip1 and increases expression level of cyclin D1 which may promote proliferation of CRC cells [25]. MiR-224 inhibits the expression of PPP2R1B, which most likely results in the change of the AKT signaling pathway and increasing the cell abilities of proliferation and even migration and invasion in HCC [26]. Furthermore, miR-224 promotes TGF-β-induced cell proliferation by targeting Smad4.…”

An Artificially Designed Interfering lncRNA Expressed by Oncolytic Adenovirus Competitively Consumes OncomiRs to Exert Antitumor Efficacy in Hepatocellular Carcinoma

“…These miRNAs execute different biologic functions through acting on different target genes and different signal transduction pathways during the occurrence and development of HCC. These miRNAs can be categorized according to their functions as follows: miR21, miR221/222, miR224, miR17-5p/20a, miR10b, miR106b, miR151-5p, miR155, miR181a/181b, and miR184 can promote the proliferation, invasion, and metastasis of HCC cells (12)(13)(14)(15)(16)(17); miR221/222, miR224, miR10b, and miR155 can inhibit HCC cell apoptosis (13,18,19,21); and miR21, miR221/222, miR143, miR1, and miR501-5p can promote the replication of HBV, induce carcinogenesis, and enhance cancer cell proliferation (36)(37)(38).…”