PMID- 32994866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201002
IS  - 1948-9358 (Print)
IS  - 1948-9358 (Electronic)
IS  - 1948-9358 (Linking)
VI  - 11
IP  - 9
DP  - 2020 Sep 15
TI  - Analysis of long noncoding RNA-associated competing endogenous RNA network in 
      glucagon-like peptide-1 receptor agonist-mediated protection in beta cells.
PG  - 374-390
LID - 10.4239/wjd.v11.i9.374 [doi]
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) and mRNAs are widely involved in 
      various physiological and pathological processes. The use of glucagon-like 
      peptide-1 receptor agonists (GLP-1RAs) is a novel therapeutic strategy that could 
      promote insulin secretion and decrease the rate of beta-cell apoptosis in type 2 
      diabetes mellitus (T2DM) patients. However, the specific lncRNAs and mRNAs and 
      their functions in these processes have not been fully identified and elucidated. 
      AIM: To identify the lncRNAs and mRNAs that are involved in the protective effect 
      of GLP-1RA in beta cells, and their roles. METHODS: Rat gene microarray was used to 
      screen differentially expressed (DE) lncRNAs and mRNAs in beta cells treated with 
      geniposide, a GLP-1RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and 
      Genomes (KEGG) pathway enrichment analyses were performed to assess the 
      underlying functions of DE mRNAs. Hub mRNAs were filtered using the STRING 
      database and the Cytoscape plugin, CytoHubba. In order to reveal the regulatory 
      relationship between lncRNAs and hub mRNAs, their co-expression network was 
      constructed based on the Pearson coefficient of DE lncRNAs and mRNAs, and 
      competing endogenous RNA (ceRNA) mechanism was explored through miRanda and 
      TargetScan databases. RESULTS: We identified 308 DE lncRNAs and 128 DE mRNAs with 
      a fold change filter of >/= 1.5 and P value < 0.05. GO and KEGG pathway enrichment 
      analyses indicated that the most enriched terms were G-protein coupled receptor 
      signaling pathway, inflammatory response, calcium signaling pathway, positive 
      regulation of cell proliferation, and ERK1 and ERK2 cascade. Pomc, Htr2a, and 
      Agtr1a were screened as hub mRNAs using the STRING database and the Cytoscape 
      plugin, CytoHubba. This result was further verified using SwissTargetPrediction 
      tool. Through the co-expression network and competing endogenous (ceRNA) 
      mechanism, we identified seven lncRNAs (NONRATT027738, NONRATT027888, 
      NONRATT030038, etc.) co-expressed with the three hub mRNAs (Pomc, Htr2a, and 
      Agtr1a) based on the Pearson coefficient of the expression levels. These lncRNAs 
      regulated hub mRNA functions by competing with six miRNAs (rno-miR-5132-3p, 
      rno-miR-344g, rno-miR-3075, etc.) via the ceRNA mechanism. Further analysis 
      indicated that lncRNA NONRATT027738 interacts with all the three hub mRNAs, 
      suggesting that it is at a core position within the ceRNA network. CONCLUSION: We 
      have identified key lncRNAs and mRNAs, and highlighted here how they interact 
      through the ceRNA mechanism to mediate the protective effect of GLP-1RA in beta 
      cells.
CI  - (c)The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Cui, Li-Juan
AU  - Cui LJ
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China.
FAU - Bai, Tao
AU  - Bai T
AD  - Department of Endocrinology, The First Clinical Hospital of Shanxi Medical 
      University, Taiyuan 030001, Shanxi Province, China.
FAU - Zhi, Lin-Ping
AU  - Zhi LP
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China.
FAU - Liu, Zhi-Hong
AU  - Liu ZH
AD  - Department of Respiratory Medicine, The First Clinical Hospital of Shanxi Medical 
      University, Taiyuan 030001, Shanxi Province, China.
FAU - Liu, Tao
AU  - Liu T
AD  - Department of General Surgery, Shanxi Bethune Hospital, Taiyuan 030006, Shanxi 
      Province, China.
FAU - Xue, Huan
AU  - Xue H
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China.
FAU - Yang, Huan-Huan
AU  - Yang HH
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China.
FAU - Yang, Xiao-Hua
AU  - Yang XH
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China.
FAU - Zhang, Min
AU  - Zhang M
AD  - College of Pharmacy, Shanxi Medical University, Taiyuan 030001, Shanxi Province, 
      China.
FAU - Niu, Ya-Ru
AU  - Niu YR
AD  - Second Clinical Medical College, Shanxi Medical University, Taiyuan 030001, 
      Shanxi Province, China.
FAU - Liu, Yun-Feng
AU  - Liu YF
AD  - Department of Endocrinology, The First Clinical Hospital of Shanxi Medical 
      University, Taiyuan 030001, Shanxi Province, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Pharmacology, Basic Medical College, Shanxi Medical University, 
      Taiyuan 030001, Shanxi Province, China. yizhang313@163.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Diabetes
JT  - World journal of diabetes
JID - 101547524
PMC - PMC7503504
OTO - NOTNLM
OT  - Co-expression analysis
OT  - Competing endogenous RNA
OT  - Glucagon-like peptide-1 receptor agonist
OT  - Long noncoding RNA
OT  - Type 2 diabetes
OT  - beta cell
COIS- Conflict-of-interest statement: The authors declare that they have no competing 
      interests and have nothing to disclose.
EDAT- 2020/10/01 06:00
MHDA- 2020/10/01 06:01
PMCR- 2020/09/15
CRDT- 2020/09/30 06:12
PHST- 2020/04/17 00:00 [received]
PHST- 2020/04/24 00:00 [revised]
PHST- 2020/08/04 00:00 [accepted]
PHST- 2020/09/30 06:12 [entrez]
PHST- 2020/10/01 06:00 [pubmed]
PHST- 2020/10/01 06:01 [medline]
PHST- 2020/09/15 00:00 [pmc-release]
AID - 10.4239/wjd.v11.i9.374 [doi]
PST - ppublish
SO  - World J Diabetes. 2020 Sep 15;11(9):374-390. doi: 10.4239/wjd.v11.i9.374.