Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma.

Mengjia Song,Shaoyan Cheng,Yue Huang,Jieying Yang,Desheng Weng,Ailin Zhong,Hao Chen,Yan Tang,Jianxiong Zeng,Qian Zhu,Ziqi Zhou,Chaopin Yang,Qiuzhong Pan,Jingjing Zhao,Yuan Liu,Jian-Chuan Xia,Xiaocong Mo,Junyi He

doi:10.18632/aging.102468

Abstract

The abnormal expression of noncoding RNAs has attracted increasing interest in the field of hepatocellular carcinoma progression. However, the underlying molecular mechanisms mediated by noncoding RNAs in these processes are unclear. Here, we obtained the expression profiles of long noncoding RNAs, microRNAs, and mRNAs from the Gene Expression Omnibus database and identified hepatocarcinogenesis-specific differentially expressed transcripts. Next, we identified significant Gene Ontology and pathway terms that the differentially expressed transcripts involved in. Using functional analysis and target prediction, we constructed a hepatocellular carcinoma-associated deregulated competitive endogenous RNA network to reveal the potential mechanisms underlying tumor progression. By analyzing The Cancer Genome Atlas dataset, six key long noncoding RNAs showed significant association with overall survival as well as strong correlation with some microRNAs and mRNAs in the competitive endogenous RNA network. We further validated the above results and determined their diagnostic and prognostic value in clinical samples. Importantly, by large-scale analyses, we identified a cluster of long noncoding RNAs, GBAP1, MCM3AP-AS1, SLC16A1-AS1, C3P1, DIO3OS, and HNF4A-AS1 as candidate biomarkers for the diagnosis and prognosis of hepatocellular carcinoma, which will improve our understanding of competitive endogenous RNA-mediated regulatory mechanisms underlying hepatocellular carcinoma development and will provide novel therapeutic targets in the future.

Highlights

Hepatocellular carcinoma (HCC) is one of the fatal malignant tumors worldwide, especially in Asia [1]
We firstly analyzed five expression profiles to identify differentially expressed genes, long noncoding RNA (lncRNA), and miRNAs between HCC samples and normal samples based on data from the Gene Expression Omnibus (GEO) database
For the identified differentially expressed genes (DEGs), gene ontology (GO) functional enrichment analysis showed that the upregulated DEGs were most significantly associated with cell division, a process that allows cells to proliferate persistently, while the downregulated DEGs were mainly involved in the oxidationreduction process

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the fatal malignant tumors worldwide, especially in Asia [1]. Long non-coding RNAs (lncRNAs) comprise transcripts with a length of over 200 nucleotides, which are characterized by low expression in cancer, high expression in tissues, and cell-specificity [6] Despite their inability to encode proteins, lncRNAs regulate the expression of many mRNAs by acting in cis and in trans. The theory of a competing endogenous RNA (ceRNA) regulation network in cancer has been proposed [10] This hypothesis states that ceRNAs harbor MREs and bind to miRNAs in competition with their target mRNAs, leading to blockade of the silencing effect of miRNAs on their target mRNAs. Accumulating studies have confirmed that lncRNAs act as sponges to sequester and bind miRNAs in competition with mRNAs [11].

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