Molecular mechanisms of circular RNAs, transforming growth factor-β, and long noncoding RNAs in hepatocellular carcinoma.

Wenkang Shang,Yujie Li,Qike Huang,Bianca Chinembiri,Ningding Ding,Mohammad Sajjad Ibn Rashid,Gabriel Komla Adzika,Jeremiah Ong'Achwa Machuki

doi:10.1002/cam4.2553

Abstract

At the heart of hepatocellular carcinoma (HCC) lies disruption of signaling pathways at the level of molecules, genes, and cells. Non‐coding RNAs (ncRNAs) have been implicated in the disease progression of HCC. For instance, dysregulated expression of circular RNAs (circRNAs) has been observed in patients with HCC. As such, these RNAs are potential therapeutic targets and diagnostic markers for HCC. Long non‐coding RNAs (lncRNAs), a type of ncRNA, have also been recognized to participate in the initiation and progression of HCC. Transforming growth factor‐beta (TGF‐β) is another element which is now recognized to play crucial roles in HCC. It has been implicated in many biological processes such as survival, immune surveillance, and cell proliferation. In HCC, TGF‐β promotes disease progression by two mechanisms: an intrinsic signaling pathway and the extrinsic pathway. Through these pathways, it modulates various microenvironment factors such as inflammatory mediators and fibroblasts. An interesting yet‐to‐be resolved concept is whether the HCC‐promoting role of TGF‐β pathways is limited to a subset of HCC patients or it is involved in the whole process of HCC development. This review summarizes recent advancements to highlight the roles of circRNAs, lncRNAs, and TGF‐β in HCC.

Highlights

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer‐related deaths globally, which is associated with low survival rate.[1,2] Every year, an estimated 700 000 deaths due to HCC are recorded worldwide.[3]
This review aims to summarize the recent findings on the features and functions of circRNAs, TGF‐β, and Long non‐ coding RNAs (lncRNAs) in HCC
A study reported that HOTAIR orchestrated the suppression of miRNA‐218‐induced Bmi‐1 expression and enchained the signaling by P14 and P16, which led to increased hepatocarcinogenesis.[135]

Summary

Introduction

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer‐related deaths globally, which is associated with low survival rate.[1,2] Every year, an estimated 700 000 deaths due to HCC are recorded worldwide.[3].

Objectives

Results

Conclusion