Comprehensive Analysis of Competing Endogenous RNA Network Focusing on Long Noncoding RNA Involved in Cirrhotic Hepatocellular Carcinoma.

Yuli Zhang,Zhongwei Zheng,Dinggui Chen,Xianfeng Qian,Miaomiao Yang,Chunmei Long,Viswanathan Pragasam

doi:10.1155/2021/5510111

Abstract

The role of long noncoding RNAs- (lncRNAs-) associated competing endogenous RNA (ceRNA) in the field of hepatocellular carcinoma (HCC) biology is well established, but the involvement of lncRNAs competing interactions in the progression of liver cirrhosis to HCC is still unclear. We aimed to explore the differential expression profiles of lncRNAs, microRNAs (miRNA), and messenger RNAs (mRNAs) to construct a functional ceRNA network in cirrhotic HCC. The lncRNA, miRNA, and mRNA expression datasets were obtained from Gene Expression Omnibus and The Cancer Genome Atlas. Based on miRanda and TargetScan, the HCC-specific ceRNA network was constructed to illustrate the coexpression regulatory relationship of lncRNAs, miRNAs, and mRNAs. The potential prognostic indicators in the network were confirmed by survival analysis and validated by qRT-PCR. A total of 74 lncRNAs, 36 intersection miRNAs, and 949 mRNAs were differentially expressed in cirrhotic HCC samples compared with cirrhosis samples. We constructed a ceRNA network, including 47 lncRNAs, 35 miRNAs, and 168 mRNAs. Survival analysis demonstrated that 2 lncRNAs (EGOT and SERHL), 4 miRNAs, and 40 mRNAs were significantly associated with the overall survival of HCC patients. Two novel regulatory pathways, EGOT-miR-32-5p-XYLT2 axis and SERHL-miR-1269a/miR-193b-3p-BCL2L1/SYK/ARNT/CHST3/LPCAT1 axis, were built up and contribute to the underlying mechanism of HCC pathogenesis. The higher-expressed SERHL was associated with a higher risk of all-cause death. The expressions of SERHL-miR-1269a-BCL2L1 were significantly different using qRT-PCR in vitro studies. lncRNAs EGOT and SERHL might serve as effective prognostic biomarkers and potential therapeutic targets in cirrhotic HCC treatment.

Highlights

Liver cancer is the sixth most common incident carcinoma and the fourth most common cause of malignant tumor mortality [1], being estimated to be 18.1 million new patients and 9.6 million cancer-related deaths throughout the world in 2018 [2]
With the tumorigenesis of hepatocellular carcinoma (HCC) in cirrhotic patients, a total of 74 Long noncoding RNAs (lncRNAs) from GSE17967, 36 intersection miRNAs from GSE21362 and GSE63046, and 949 messenger RNAs (mRNAs) from GSE17967 were identified with the restricted criteria of FC > 1:2 and P < 0:05 by bioinformatics analysis (Figure 1)
Our study demonstrated the differential expression profiling of lncRNAs, miRNAs, and mRNAs in cirrhotic HCC

Summary

Introduction

Liver cancer is the sixth most common incident carcinoma and the fourth most common cause of malignant tumor mortality [1], being estimated to be 18.1 million new patients and 9.6 million cancer-related deaths throughout the world in 2018 [2]. Liver cirrhosis plays a vital role in the pathogenesis of HCC. Based on the cirrhosis affecting progression to HCC, specific molecular biomarkers and potential regulatory mechanisms are essential and meaningful to the early diagnosis, treatment strategies, and the evaluation of prognosis. Long noncoding RNAs (lncRNAs) are endogenous noncoding RNA molecules more than 200 nucleotides in length and can be subclassified into exonic, intronic, overlapping, and intergenic lncRNAs in nuclear or cytosolic fractions [5]. Given their regulation of cell proliferation, apoptosis, Analytical Cellular Pathology

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