{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:53:36Z","timestamp":1778882016350,"version":"3.51.4"},"reference-count":95,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>For a global epidemic like Type 2 diabetes mellitus (T2DM), while impaired gene regulation is identified as a primary cause of aberrant cellular physiology; in the past few years, non-coding RNAs (ncRNAs) have emerged as important regulators of cellular metabolism. However, there are no reports of comprehensive in-depth cross-talk between these regulatory elements and the potential consequences in the skeletal muscle during diabetes. Here, using RNA sequencing, we identified 465 mRNAs and 12 long non-coding RNAs (lncRNAs), to be differentially regulated in the skeletal muscle of diabetic mice and pathway enrichment analysis of these altered transcripts revealed pathways of insulin, FOXO and AMP-activated protein kinase (AMPK) signaling to be majorly over-represented. Construction of networks showed that these pathways significantly interact with each other that might underlie aberrant skeletal muscle metabolism during diabetes. Gene\u2013gene interaction network depicted strong interactions among several differentially expressed genes (DEGs) namely, Prkab2, Irs1, Pfkfb3, Socs2 etc. Seven altered lncRNAs depicted multiple interactions with the altered transcripts, suggesting possible regulatory roles of these lncRNAs. Inverse patterns of expression were observed between several of the deregulated microRNAs (miRNAs) and the differentially expressed transcripts in the tissues. Towards validation, overexpression of miR-381-3p and miR-539-5p in skeletal muscle C2C12 cells significantly decreased the transcript levels of their targets, Nfkbia, Pik3r1 and Pi3kr1, Cdkn2d, respectively. Collectively, the findings provide a comprehensive understanding of the interactions and cross-talk between the ncRNome and transcriptome in the skeletal muscle during diabetes and put forth potential therapeutic options for improving insulin sensitivity.<\/jats:p>","DOI":"10.1042\/bsr20210495","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T18:44:02Z","timestamp":1625078642000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["RNA sequencing reveals potential interacting networks between the altered transcriptome and ncRNome in the skeletal muscle of diabetic mice"],"prefix":"10.1042","volume":"41","author":[{"given":"Devesh","family":"Kesharwani","sequence":"first","affiliation":[{"name":"CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, Mall Road, Delhi, India"},{"name":"Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, Ghaziabad 201002, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, Mall Road, Delhi, India"},{"name":"Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, Ghaziabad 201002, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukta","family":"Poojary","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, Ghaziabad 201002, Uttar Pradesh, India"},{"name":"GN Ramachandran Knowledge Centre for Genome Informatics, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinod","family":"Scaria","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, Ghaziabad 201002, Uttar Pradesh, India"},{"name":"GN Ramachandran Knowledge Centre for Genome Informatics, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110025, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2559-9991","authenticated-orcid":false,"given":"Malabika","family":"Datta","sequence":"additional","affiliation":[{"name":"CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, Mall Road, Delhi, India"},{"name":"Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, Ghaziabad 201002, Uttar Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"2021111620493974600_B1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. 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