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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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12859-020-03678-0","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:03:04Z","timestamp":1600300984000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi-omics profiling reveals microRNA-mediated insulin signaling networks"],"prefix":"10.1186","volume":"21","author":[{"given":"Yang-Chi-Dung","family":"Lin","sequence":"first","affiliation":[]},{"given":"Hsi-Yuan","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Sirjana","family":"Shrestha","sequence":"additional","affiliation":[]},{"given":"Chih-Hung","family":"Chou","sequence":"additional","affiliation":[]},{"given":"Yen-Hua","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Chi-Ru","family":"Chen","sequence":"additional","affiliation":[]},{"given":"Hsiao-Chin","family":"Hong","sequence":"additional","affiliation":[]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[]},{"given":"Yi-An","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Men-Yee","family":"Chiew","sequence":"additional","affiliation":[]},{"given":"Ya-Rong","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Siang-Jyun","family":"Tu","sequence":"additional","affiliation":[]},{"given":"Ting-Hsuan","family":"Sun","sequence":"additional","affiliation":[]},{"given":"Shun-Long","family":"Weng","sequence":"additional","affiliation":[]},{"given":"Ching-Ping","family":"Tseng","sequence":"additional","affiliation":[]},{"given":"Hsien-Da","family":"Huang","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"issue":"2","key":"3678_CR1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel DP. 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