Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma

Li Guo; Yuyang Dou; Yifei Yang; Shiqi Zhang; Yihao Kang; Lulu Shen; Lihua Tang; Yaodong Zhang; Changxian Li; Jun Wang; Tingming Liang; Xiangcheng Li

doi:10.1016/j.csbj.2021.10.014

Protein profiling reveals potential isomiR-associated cross-talks among RNAs in cholangiocarcinoma

Comput Struct Biotechnol J. 2021 Oct 14:19:5722-5734. doi: 10.1016/j.csbj.2021.10.014. eCollection 2021.

Authors

Li Guo¹, Yuyang Dou¹, Yifei Yang^{1

2}, Shiqi Zhang^{1

2}, Yihao Kang¹, Lulu Shen³, Lihua Tang¹, Yaodong Zhang⁴, Changxian Li⁴, Jun Wang¹, Tingming Liang³, Xiangcheng Li⁴

Affiliations

¹ Department of Bioinformatics, Smart Health Big Data Analysis and Location Services Engineering Lab of Jiangsu Province, School of Geographic and Biologic Information, Nanjing University of Posts and Telecommunications, Nanjing 210023, China.
² Department of Biology, Brandeis University, Waltham, MA, USA.
³ Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China.
⁴ Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Abstract

Cholangiocarcinomas (CCAs) are tumors that arise from the cholangiocytes. Although some genes have been shown with important roles in pathological process, interactions or cross-talks among different RNAs are important to understand the detailed molecular mechanisms in cancer development, especially discussing cross-talks among isomiRs and other RNAs. Herein, to characterize crucial genes in CCA, the protein expression profile was performed to survey potential crucial mRNAs and related non-coding RNAs (ncRNAs) in mRNA-ncRNA network, mainly including miRNAs/isomiRs and lncRNAs. Deregulated mRNAs were firstly obtained if consistent expression patterns were found at protein and mRNA levels, and related miRNAs/isomiRs were screened according to regulatory relationships. Diverse isomiRs from a given miRNA locus also contributed to interactions between the small RNAs and target mRNAs, and miRNAs were further used to survey related lncRNAs to expand the interactions. Thus, several groups of RNAs were constructed as candidate competitive endogenous RNA (ceRNA) networks. Finally, we found that RAB11FIP1:miR-101-3p:MIR3142HG may be a potential ceRNA network, and the interactions among them may be more complex due to variety of isomiRs. Simultaneously, RAB11FIP1 and miR-194-5p were also detected other related lncRNAs (FBXL19-AS1, SNHG1 and PVT1) that may be crucial in coding-non-coding RNA regulatory network. Our results show that diverse isomiRs with sequence and expression heterogeneities contribute to ceRNA regulatory network that may have crucial roles in CCA, which will expand our understanding of interactions among diverse RNAs and their contributions in cancer development.

Keywords: BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; Cholangiocarcinoma (CCA); Cross-talk; ESCA, esophageal carcinoma; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, Kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; Long non-coding RNA (lncRNA); PRAD, prostate adenocarcinoma; Protein profiling; STAD, stomach adenocarcinoma; THCA, thyroid carcinoma; UCEC, uterine corpus endometrial carcinoma; isomiR; microRNA (miRNA).