NOV/CCN3 Promotes Cell Migration and Invasion in Intrahepatic Cholangiocarcinoma via miR-92a-3p.

Tingming Liang,Li Guo,Yuyang Dou,Lin Jia,Lulu Shen,Yaya Ji

doi:10.3390/genes12111659

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a common type of human cancer with a poor prognosis, and investigating the potential molecular mechanisms that can contribute to gene diagnosis and therapy. Herein, based on the recently concerned vertebrate-specific Cyr61/CTGF/NOV (CCN) gene family because of its important roles in diverse diseases, we obtained NOV/CCN3 to query for its potential roles in tumorigenesis via bioinformatics analysis. Experimental validations confirmed that both NOV mRNA and protein are up-regulated in two ICC cell lines, suggesting that it may promote cell migration and invasion by promoting EMT. To elucidate the detailed regulatory mechanism, miR-92a-3p is screened and identified as a negative regulatory small RNA targeting NOV, and further experimental validation demonstrates that miR-92a-3p contributes to NOV-mediated migration and invasion of ICC via the Notch signaling pathway. Our study reveals that NOV may be a potential target for diagnosing and treating ICC, which will provide experimental data and molecular theoretical foundation for cancer treatment, particularly for future precision medicine.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Several members in the CCN gene family have been implicated in critical biological processes, most notably cancer hallmarks [40,41]
WISP1, WISP2, and WISP3 are members in the insensitivity to antigrowth signals, self-sufficiency in growth signals, tissue invasion and metastasis, and CTGF is a member in self-sufficiency in growth signals and tissue invasion and metastasis, while NOV is a member in the insensitivity to antigrowth signals

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Intrahepatic cholangiocarcinoma (ICC), a refractory liver malignancy, is one of the most common cancers, and patients diagnosed with ICC are challenging to cure with poor prognosis [1]. The median survival time of patients is less than 24 months [2].

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