PMID- 34190986
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20240226
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 41
IP  - 7
DP  - 2021 Jul 30
TI  - RNA sequencing reveals potential interacting networks between the altered 
      transcriptome and ncRNome in the skeletal muscle of diabetic mice.
LID - 10.1042/BSR20210495 [doi]
LID - BSR20210495
AB  - 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-gene 
      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.
CI  - (c) 2021 The Author(s).
FAU - Kesharwani, Devesh
AU  - Kesharwani D
AD  - CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, 
      Mall Road, Delhi, India.
AD  - Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, 
      Ghaziabad 201002, Uttar Pradesh, India.
FAU - Kumar, Amit
AU  - Kumar A
AD  - CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, 
      Mall Road, Delhi, India.
AD  - Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, 
      Ghaziabad 201002, Uttar Pradesh, India.
FAU - Poojary, Mukta
AU  - Poojary M
AD  - Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, 
      Ghaziabad 201002, Uttar Pradesh, India.
AD  - GN Ramachandran Knowledge Centre for Genome Informatics, CSIR-Institute of 
      Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
FAU - Scaria, Vinod
AU  - Scaria V
AD  - Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, 
      Ghaziabad 201002, Uttar Pradesh, India.
AD  - GN Ramachandran Knowledge Centre for Genome Informatics, CSIR-Institute of 
      Genomics and Integrative Biology, Mathura Road, Delhi 110025, India.
FAU - Datta, Malabika
AU  - Datta M
AUID- ORCID: 0000-0002-2559-9991
AD  - CSIR-Institute of Genomics and Integrative Biology, Functional and Genomics Unit, 
      Mall Road, Delhi, India.
AD  - Academy of Scientific and Innovative Research, CSIR-HRDC, Kamala Nehru Nagar, 
      Ghaziabad 201002, Uttar Pradesh, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Insulin)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Diabetes Mellitus/*genetics/metabolism
MH  - Disease Models, Animal
MH  - *Gene Expression Profiling
MH  - *Gene Regulatory Networks
MH  - Insulin/metabolism
MH  - Insulin Resistance/genetics
MH  - Male
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics/metabolism
MH  - Muscle, Skeletal/*metabolism
MH  - RNA, Long Noncoding/*genetics/metabolism
MH  - RNA, Messenger/*genetics/metabolism
MH  - *RNA-Seq
MH  - Signal Transduction
MH  - *Transcriptome
MH  - Mice
PMC - PMC8276098
OTO - NOTNLM
OT  - RNA sequencing
OT  - diabetes
OT  - ncRNA
OT  - skeletal muscle
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2021/07/01 06:00
MHDA- 2022/02/01 06:00
PMCR- 2021/07/12
CRDT- 2021/06/30 12:26
PHST- 2021/03/05 00:00 [received]
PHST- 2021/06/21 00:00 [revised]
PHST- 2021/06/29 00:00 [accepted]
PHST- 2021/07/01 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/06/30 12:26 [entrez]
PHST- 2021/07/12 00:00 [pmc-release]
AID - 229124 [pii]
AID - BSR20210495 [pii]
AID - 10.1042/BSR20210495 [doi]
PST - ppublish
SO  - Biosci Rep. 2021 Jul 30;41(7):BSR20210495. doi: 10.1042/BSR20210495.