Interplay of miRNAs and Canonical Wnt Signaling Pathway in Hepatocellular Carcinoma.

Wei-Dong Chen,Yan-Dong Wang,Xiaobo Nie,Yiran Liu

doi:10.3389/fphar.2018.00657

Abstract

Hepatocellular carcinoma is one of the leading causes of cancer death worldwide and the activation of canonical Wnt signaling pathway is universal in hepatocellular carcinoma patients. MicroRNAs are found to participate in the pathogenesis of hepatocellular carcinoma by activating or inhibiting components in the canonical Wnt signaling pathway. Meanwhile, transcriptional activation of microRNAs by canonical Wnt signaling pathway also contributes to the occurrence and progression of hepatocellular carcinoma. Pharmacological inhibition of hepatocellular carcinoma pathogenesis and other cancers by microRNAs are now in clinical trials despite the challenges of identifying efficient microRNAs candidates and safe delivery vehicles. The focus of this review is on the interplay mechanisms between microRNAs and canonical Wnt signaling pathway in hepatocellular carcinoma, and a deep understanding of the crosstalk will promote to develop a better management of this disease.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer death worldwide, with more than 750,000 new cases diagnosed and 700,000 cancer deaths occurred annually
As a secreted lipid binding protein that binds to Wnt proteins and inhibits Wnt signaling pathway, Wnt inhibitory factor1 (WIF-1) is identified as a direct and functional target of miR-181a in colorectal cancer, and an ectopic expression of miR-181a promotes tumor growth and liver metastasis (Ji et al, 2014)
Sun’s group has reported that miR-522 promotes cell proliferation of HCC by targeting DKK1 and secreted frizzled-related protein 2 (SFRP2) and activating Wnt signaling (Zhang H. et al, 2016), whereas other researchers report that DDK1 is overexpressed in HCC cells and tissues, and promotes HCC cell migration and invasion through β-catenin/MMP7 pathway (Chen L. et al, 2013)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of cancer death worldwide, with more than 750,000 new cases diagnosed and 700,000 cancer deaths occurred annually. MiR122 expression level is found to be decreased significantly in human HCC tissue samples and cell lines, and overexpression of miR-122 inhibits proliferation but promotes hepatoma cell apoptosis by repressing Wnt1 expression, subsequently leads to blocking Wnt1/β-catenin/TCF signaling pathway (Xu J. et al, 2012; Ahsani et al, 2017) (Table 1).

Results

Conclusion