PMID- 35761309
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1758-5996 (Print)
IS  - 1758-5996 (Electronic)
IS  - 1758-5996 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Jun 27
TI  - Targeting ferroptosis with miR-144-3p to attenuate pancreatic beta cells dysfunction 
      via regulating USP22/SIRT1 in type 2 diabetes.
PG  - 89
LID - 10.1186/s13098-022-00852-7 [doi]
LID - 89
AB  - BACKGROUND: Recently, ferroptosis has been implicated in the pathologic process 
      of several diseases including type 2 diabetes mellitus (T2DM). However, molecular 
      mechanisms underlying ferroptosis in T2DM remain obscure. METHODS: Twenty four 
      mice were included in this study. T2DM model mice were established by a high-fat 
      diet combined with streptozotocin injection. INS-1 cells were stimulated with 
      high glucose (HG). Cell viability was detected by CCK-8 kit. The levels of GSH, 
      MDA, iron, and lipid ROS, and SOD activity, were detected by the corresponding 
      kits. The interaction between miR-144-3p and USP22 was validated by 
      dual-luciferase reporter assay. The relationship between USP22 and its substrate 
      was verified using Co-IP and ubiquitination assays. The mRNA and protein 
      expressions were examined by RT-qPCR and western blot, respectively. The 
      functions of beta cells in vitro and in vivo were evaluated glucose-stimulated 
      insulin secretion test and HOMA-beta, respectively. RESULTS: Ferroptosis occurred in 
      the pancreas of T2DM mice and HG-induced INS-1 cells. Silencing miR-144-3p 
      blocked the effect of HG on the cell viability and accumulation of lipid 
      peroxides, thereby improving the insulin secretion in INS-1 cells. 
      Mechanistically, USP22 is a direct target of miR-144-3p, which could stabilize 
      SIRT1 expression, thereby suppressing ferroptosis. Overexpressing USP22 
      attenuated deleterious roles of HG in INS-1 cells; but its roles were reversed by 
      up-regulating miR-144-3p. In vivo study demonstrated that miR-144-3p antagomir 
      exerted an anti-hyperglycemic effect and regulated the ferroptosis-related 
      proteins in the pancreas. CONCLUSION: The up-regulation of miR-144-3p suppressed 
      USP22/SIRT1 to induce ferroptosis, which causes pancreatic beta cells dysfunction, 
      thereby promoting T2DM development.
CI  - (c) 2022. The Author(s).
FAU - Zhang, Shanshan
AU  - Zhang S
AD  - School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, 
      Xincheng District, Pingdingshan, 467000, Henan, China.
AD  - Shool of Nursing, Doctor of Philosophy in Nursing, Philippine Women's University, 
      Manila, Philippines.
FAU - Liu, Xiao
AU  - Liu X
AD  - School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, 
      Xincheng District, Pingdingshan, 467000, Henan, China. sszh.baobao@163.com.
AD  - Shool of Nursing, Doctor of Philosophy in Nursing, Philippine Women's University, 
      Manila, Philippines. sszh.baobao@163.com.
FAU - Wang, Jihong
AU  - Wang J
AD  - School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, 
      Xincheng District, Pingdingshan, 467000, Henan, China. 799981507@qq.com.
FAU - Yuan, Fengjuan
AU  - Yuan F
AD  - School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, 
      Xincheng District, Pingdingshan, 467000, Henan, China.
AD  - Shool of Nursing, Doctor of Philosophy in Nursing, Philippine Women's University, 
      Manila, Philippines.
FAU - Liu, Yali
AU  - Liu Y
AD  - School of Medicine of Pingdingshan University, Middle Section of Chongwen Road, 
      Xincheng District, Pingdingshan, 467000, Henan, China.
AD  - Shool of Nursing, Doctor of Philosophy in Nursing, Philippine Women's University, 
      Manila, Philippines.
LA  - eng
GR  - wjlx2020293/medical education research project of Henan Province, based on the 
      construction of the elderly nursing technology curriculum system based on the 
      post competency training of elderly nursing talents, project number/
GR  - jpzx19247/Pingdingshan University Health Assessment School-level Excellent Online 
      Open Course/
PT  - Journal Article
DEP - 20220627
PL  - England
TA  - Diabetol Metab Syndr
JT  - Diabetology & metabolic syndrome
JID - 101488958
PMC - PMC9235078
OTO - NOTNLM
OT  - Ferroptosis
OT  - Pancreatic beta cells
OT  - Type 2 diabetes mellitus
OT  - USP22
OT  - miR-144-3p
COIS- The authors declare that they have no competing interests.
EDAT- 2022/06/28 06:00
MHDA- 2022/06/28 06:01
PMCR- 2022/06/27
CRDT- 2022/06/27 23:45
PHST- 2022/02/15 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/06/27 23:45 [entrez]
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/06/28 06:01 [medline]
PHST- 2022/06/27 00:00 [pmc-release]
AID - 10.1186/s13098-022-00852-7 [pii]
AID - 852 [pii]
AID - 10.1186/s13098-022-00852-7 [doi]
PST - epublish
SO  - Diabetol Metab Syndr. 2022 Jun 27;14(1):89. doi: 10.1186/s13098-022-00852-7.