PMID- 34733939
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220428
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 17
DP  - 2021 Sep
TI  - LncRNA KCNQ1OT1 promoted hepatitis C virus-induced pyroptosis of beta-cell through 
      mediating the miR-223-3p/NLRP3 axis.
PG  - 1387
LID - 10.21037/atm-21-3862 [doi]
LID - 1387
AB  - BACKGROUND: Type 2 diabetes is a well described extra-hepatic manifestation of 
      hepatitis C virus (HCV) infection. This study aimed to explore the potential 
      mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in type 2 diabetes 
      mellitus (T2DM) caused by HCV infection. METHODS: Min6 cells were infected with 
      HCV to establish a vitro model, and the HCV copy number was detected by real-time 
      quantitative PCR (RT-qPCR). The mRNA and protein expressions of IL-1beta, IL-18, 
      NLRP3, caspase-1, and GSDMD were analyzed by RT-qPCR and Western blot. Flow 
      cytometry and TUNEL assay were used to evaluate the pyroptosis of cells and 
      enzyme-linked immunosorbent assay (ELISA) detected the secretion of insulin. A 
      dual luciferase reporter gene assay then verified the targeting relationship of 
      KCNQ1OT1, miRNA-223-3p, and NLRP3. RESULTS: KCNQ1OT1 was highly expressed in 
      HCV-infected T2DM patients and HCV-infected beta-cells. Silencing KCNQ1OT1 inhibited 
      beta-cell pyroptosis by regulating miR-223-3p/NLRP3, and inhibition of miR-223-3p or 
      overexpression of NLRP3 reversed the pyroptosis by silencing KCNQ1OT1. 
      CONCLUSIONS: Our findings indicate KCNQ1OT1 promotes HCV-infected beta-cell 
      pyroptosis through the miRNA-223-3p/NLRP3 axis, effecting the production of 
      insulin and accelerating the occurrence and development of T2DM.Regulating 
      KCNQ1OT1 and its target genes will help to better understand the pathogenesis of 
      T2DM induced by HCV infection and provide new theoretical foundations and 
      therapeutic targets.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - Niu, Ben
AU  - Niu B
AD  - Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan 
      Province, The Affiliated Hospital of Kunming University of Science and 
      Technology, Kunming, China.
FAU - Yao, Lixuan
AU  - Yao L
AD  - Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan 
      Province, The Affiliated Hospital of Kunming University of Science and 
      Technology, Kunming, China.
FAU - Zhang, Yating
AU  - Zhang Y
AD  - Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan 
      Province, The Affiliated Hospital of Kunming University of Science and 
      Technology, Kunming, China.
FAU - Xia, Xueshan
AU  - Xia X
AD  - Faculty of Life Science and Technology, Kunming University of Science and 
      Technology, Kunming, China.
FAU - Su, Heng
AU  - Su H
AD  - Department of Endocrinology and Metabolism, The First People's Hospital of Yunnan 
      Province, The Affiliated Hospital of Kunming University of Science and 
      Technology, Kunming, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8506540
OTO - NOTNLM
OT  - KCNQ1 overlapping transcript 1 (KCNQ1OT1)
OT  - hepatitis C virus (HCV)
OT  - miR-223-3p
OT  - pyroptosis
OT  - beta-cell
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-3862). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/11/05 06:00
MHDA- 2021/11/05 06:01
PMCR- 2021/09/01
CRDT- 2021/11/04 06:28
PHST- 2021/07/01 00:00 [received]
PHST- 2021/08/12 00:00 [accepted]
PHST- 2021/11/04 06:28 [entrez]
PHST- 2021/11/05 06:00 [pubmed]
PHST- 2021/11/05 06:01 [medline]
PHST- 2021/09/01 00:00 [pmc-release]
AID - atm-09-17-1387 [pii]
AID - 10.21037/atm-21-3862 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Sep;9(17):1387. doi: 10.21037/atm-21-3862.