Role of LncRNAs in the Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

Xiaoyong Ge,Jing Li,Zhaonan Li,Xinwei Han,Yuan Yao

doi:10.3389/fonc.2021.690800

Xiaoyong Ge, Jing Li + Show 3 more

Open Access

https://doi.org/10.3389/fonc.2021.690800

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Abstract

Hepatocellular carcinoma (HCC) is a type of primary liver cancer with a high incidence and mortality rate. HCC develops insidiously, and most newly diagnosed cases are in the middle and advanced stages. The epithelial-mesenchymal transition (EMT) is a vital mechanism underlying metastasis in patients with advanced HCC. EMT is a multistep and complex procedure. The promotion and inhibition of EMT directly affect the migration and invasion of HCC. LncRNAs are involved in the epigenetic modification of genes, regulation of gene transcription, and posttranslational modification of proteins. LncRNAs also play important roles in regulating EMT progression in HCC and are promising biomarkers and therapeutic targets. This review focused on summarizing the mechanism by which lncRNAs regulate EMT in HCC. In particular, lncRNAs were reported to primarily act as RNA sponges, and the regulation of EMT involves major signaling pathways. Finally, we reviewed the mechanisms by which lncRNAs are involved in drug resistance and discussed the clinical prospects and potential challenges of utilizing lncRNAs to treat HCC.

Highlights

Primary liver cancer was the sixth-highest morbidity and third-highest cancer-related mortality worldwide, with 905,677 (4.7% morbidity) new cases and 830,180 (8.3% mortality) deaths according to the Global Cancer Observatory (GCO) [1] in 2020
bone morphogenetic protein 1 (BMP1), the downstream target gene of miR-29c, is an oncogene whose overexpression can stimulate the mitogen-activated protein kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway and promote Epithelial– mesenchymal transition (EMT). These findings indicated that HOXA-AS3 upregulated BMP1 by sponging miR-29c, thereby activating the mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathway to enhance EMT
C-Myb is a proto-oncogene that regulates the MEK/ERK signaling pathway. These findings indicated that the Long noncoding RNA (lncRNA) DRHC bound to MYB Binding Protein 1a (MYBBP1A) and formed a lncRNA/DRHC/MYBBP1A/c-Myb complex with c-Myb to inhibit the MEK/ERK signaling pathway and inhibit EMT

Summary

INTRODUCTION

Primary liver cancer was the sixth-highest morbidity and third-highest cancer-related mortality worldwide, with 905,677 (4.7% morbidity) new cases and 830,180 (8.3% mortality) deaths according to the Global Cancer Observatory (GCO) (https://gco.iarc.fr/) [1] in 2020. Epithelial– mesenchymal transition (EMT) plays a vital role in the development, invasion, and metastasis of growing tumors, including HCC [4]. Role of LncRNAs in EMT of HCC important role in the process of EMT in tumor tissues, which has been revealed in prior research [6]. Increasing evidence shows that lncRNAs play a vital role in the regulation of EMT signaling pathways in tumor tissue. LncRNAs are generally considered functional regulatory factors, but recent studies have shown that lncRNAs can encode certain small peptides and play biological roles in a subset of tissues, including tumors [18]. LncRNAs are abnormally expressed in tumor cells and play an important regulatory role in tumor proliferation in such cancers as hepatocellular carcinoma [22], breast cancer [23], and gastric cancer [24]. To the best of our knowledge, there has not been a review on the role of lncRNAs in EMT in HCC

LNCRNAS INVOLVEMENT IN EMT OF HCC

LncRNAs Regulation of EMT via the Positive Feedback Loop

RNA sponges RNA sponges

LncRNAs Regulation of EMT via Other Signaling Pathways

PROSPECT OF LNCRNAS

Overexpressed Overexpressed