Multi-omics profiling reveals microRNA-mediated insulin signaling networks
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RESEARCH
Open Access
Multi-omics profiling reveals microRNAmediated insulin signaling networks Yang-Chi-Dung Lin1,2†, Hsi-Yuan Huang1,2†, Sirjana Shrestha3,4, Chih-Hung Chou3,4, Yen-Hua Chen5, Chi-Ru Chen4, Hsiao-Chin Hong1,2, Jing Li1,2, Yi-An Chang3, Men-Yee Chiew4, Ya-Rong Huang3, Siang-Jyun Tu3, Ting-Hsuan Sun4, Shun-Long Weng6, Ching-Ping Tseng4* and Hsien-Da Huang1,2,4* From The 18th Asia Pacific Bioinformatics Conference Seoul, Korea. 18-20 August 2020
* Correspondence: [email protected]. edu.tw; [email protected] † Yang-Chi-Dung Lin and Hsi-Yuan Huang contributed equally to this work. 4 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 300, Taiwan 1 School of Life and Health Sciences, The Chinese University of Hong Kong, Longgang District, Shenzhen 518172, Guangdong Province, China Full list of author information is available at the end of the article
Abstract Background: MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells. Results: We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network. Conclusions: In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes. Keywords: miRNA, Pancreatic beta-cell, RNA-seq, Multi-omics
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduct
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