MicroRNA-153 promotes Wnt/β-catenin activation in hepatocellular carcinoma through suppression of WWOX

Abstract

Persistent activation of Wnt/β-catenin signaling plays crucial roles in the development of human cancers, including hepatocellular carcinoma (HCC). Here, we performed a MicroRNA-based genetic screen, which revealed a novel diversion in β-catenin signaling triggered by MicroRNA-153 (miR-153). Overexpression of miR-153 was able to promote β-catenin transcriptional activity, leading to cell-cycle progression, proliferation and colony formation of HCC cells. Additionally, systemic administration of miR-153 antigomir suppressed hepatocellular carcinogenesis in a murine liver cancer model. At the molecular level, we found that miR-153 inhibited protein level of WWOX, a tumor suppressor and inhibitor of β-catenin signaling, through targeting its 3′-untranslated region. Therefore, our study highlights the importance of MicroRNA-153/WWOX/β-catenin regulatory axis in the HCC tumorigenesis.

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

“…Then western blot assay was performed as described previously. 45 The levels of protein were normalized to total GAPDH.…”

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma

“…Most dying cells may have already been cleared by the time we collected tumors; if so, their mRNA was not captured. Alternatively, phenotypic and functional differences between grow and regress tumor cells may be caused by diverse expression of miRNAs, frequently reported to impact HCC . Our RNA‐seq data only includes mRNA, so this could not be assessed in this study.…”

“…Alternatively, phenotypic and functional differences between grow and regress tumor cells may be caused by diverse expression of miRNAs, frequently reported to impact HCC. [43][44][45][46] Our RNA-seq data only includes mRNA, so this could not be assessed in this study.…”

microRNA regulation of Wnt signaling pathways in development and disease

“…Although not directly targeting the Wnt pathway, upregulated oncogenic miR-130a directly inhibits tumor suppressor Runx3 expression which results in activation of Wnt/β-catenin signaling and HCC resistance to cisplatin, a commonly used chemotherapeutic drug used for treatment [311]. Recently, oncogenic miR-153 was identified to regulate a tumor suppressor WWOX, inhibitor of the Wnt/β-catenin signaling pathway [312]. Overexpression of miR-153 leads to increased proliferation in HCC in a murine liver cancer model.…”