LncRNA-miRNA-mRNA Networks of Gastrointestinal Cancers Representing Common and Specific LncRNAs and mRNAs.

Hassan Dastsooz,Hamed Haghi-Aminjan,Asieh Hosseini,Parham Habibzadeh,Ahad Alizadeh,Ali Nariman,Yaser Mansoori

doi:10.3389/fgene.2021.791919

Abstract

Gastrointestinal (GI) cancers are responsible for approximately half of cancer-related deaths, highlighting the need for the identification of distinct and common features in their clinicopathological characteristics. Long ncRNA (lncRNAs), which are involved in competitive endogenous RNA (ceRNA) networks with critical roles in biological processes, constitute a substantial number of non-coding RNAs. Therefore, our study aimed to investigate the similarities and differences in the ceRNA networks of The Cancer Genome Atlas (TCGA)-GI cancers. We performed a comprehensive bioinformatics analysis of ceRNA networks for TCGA-GI cancers in terms of the deferential mRNA, lncRNA, and miRNA expression levels, ceRNA networks, overall survival analysis, correlation analysis, pathological cancer stages, and gene set enrichment analysis. Our study revealed several common and distinct mRNAs and lncRNAs with prognostic values in these networks. It was specifically noteworthy that MAGI2-AS3 lncRNA was found to be shared in almost all GI cancers. Moreover, the most common shared mRNAs between GI cancers were MEIS1, PPP1R3C, ADAMTSL3, RIPOR2, and MYLK. For each cancer ceRNA network, we found that the expression level of a number of lncRNAs and mRNAs was specific. Furthermore, our study provided compelling evidence that several genes, most notably KDELC1, can act as novel proto-oncogenes in cancers. This, in turn, can highlight their role as new prognostic and therapeutic targets. Moreover, we found cell cycle and extracellular matrix structural constituent as the top shared KEGG and molecular function, respectively, among GI cancers. Our study revealed several known lncRNAs and known and unknown mRNAs in GI cancers with diagnostic and prognostic values.

Highlights

The gastrointestinal (GI) system consists of the substantial cellular mass in the human body, and its cancers are among the most common malignancies in different populations, accounting for 35% of the total deaths due to cancers (Arnold et al, 2020)
Our study revealed the following numbers of differentially expressed mRNAs (DEmRNAs), long ncRNAs (lncRNAs) (DElncRNA), and miRNAs (DemiRNAs) maintained in the competitive endogenous RNA (ceRNA) networks of each cancer (Supplementary Table S1): head and neck squamous cell carcinoma (HNSC) (6 lncRNAs, 30 miRNAs, and 64 mRNAs), esophageal carcinoma (ESCA) (4 lncRNAs, 17 miRNAs, and 15 mRNAs), colon adenocarcinoma (COAD) [9 lncRNAs, 37 miRNAs, and 71 mRNAs, the ceRNA network for COAD cancer was previously shown in a different way (Poursheikhani et al, 2020)], stomach adenocarcinoma (STAD) (4 lncRNAs, 18miRNAs, and 29 mRNAs), rectal adenocarcinoma (READ) (9 lncRNAs, 21miRNAs, and 45 mRNAs), and liver hepatocellular carcinoma (LIHC) [10 lncRNAs, 30 miRNAs, and 64 mRNAs, its ceRNA network was shown in a different figure by Zheng and Yu (2021)] (Supplementary Table S1)
Our findings showed that LIHC, COAD, and READ had more ceRNA networks

Summary

Introduction

The gastrointestinal (GI) system consists of the substantial cellular mass in the human body, and its cancers are among the most common malignancies in different populations, accounting for 35% of the total deaths due to cancers (Arnold et al, 2020). Increasing evidence has shown that lncRNAs are involved in competitive endogenous RNA (ceRNA) networks playing critical biological functions including the regulation of major cellular processes, namely, proliferation, differentiation, apoptosis, and stress response (Niu et al, 2020b; Li et al, 2021). Our study aimed to investigate the similarities and differences in the ceRNA networks of TCGA-GI cancers with more focus on lncRNAs. We included GI cancers with 11 and more than 11 matched normal tissues. We included GI cancers with 11 and more than 11 matched normal tissues These cancers were as follows: colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), head and neck squamous cell carcinoma (HNSC), and liver hepatocellular carcinoma (LIHC). Since HNSC is involved in the mucosa of the aero-digestive tract and occurs in the oral cavity and salivary glands, we considered this cancer in our study as well

Methods

Results

Conclusion