PMID- 33792838
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20220531
IS  - 0975-0711 (Electronic)
IS  - 0254-8860 (Linking)
VI  - 40
IP  - 2
DP  - 2021 Apr
TI  - miR-222 regulates cell growth, apoptosis, and autophagy of interstitial cells of 
      Cajal isolated from slow transit constipation rats by targeting c-kit.
PG  - 198-208
LID - 10.1007/s12664-020-01143-7 [doi]
AB  - BACKGROUND: Excessive autophagy and apoptosis of the interstitial cells of Cajal 
      (ICC) have been identified in gastrointestinal (GI) motility disorders including 
      slow transit constipation (STC). MicroRNA 222 (miR-222) has been shown to affect 
      GI motility. This study aimed to explore whether miR-222 influences apoptosis and 
      excessive autophagy of isolated ICC. METHODS: miR-222, c-kit, and stem cell 
      factor (SCF) were evaluated in colon tissues in STC rats compared with normal 
      control by qRT-PCR and western blot analysis. The condition of autophagy of colon 
      tissue was observed by transmission electron microscope. ICC were isolated from 
      the colon of STC rats. Cell Counting Kit-8 (CCK-8) assay and wound healing assay 
      were carried out to examine the cell viability and migration rate. Cell apoptosis 
      was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling 
      (TUNEL) and Annexin V-Flourescein Isothiocyanate/Propidine Iodide 
      (FITC/PI) apoptosis detection kit. Western blot analysis was performed to detect 
      the c-kit and SCF expression; apoptosis-related proteins Bcl-2, Bax, caspase-3, 
      and pro-caspase-3; and autophagy-related proteins LC3B and Beclin-1. The 
      connection between miR-222 and c-kit was detected by bioinformatics and 
      luciferase activity analysis. RESULTS: miR-222 expression was significantly 
      higher, whereas c-kit and SCF expressions were markedly lower in STC rats' colon 
      tissue compared with normal control. Meanwhile, STC rats exhibited excessive 
      autophagy in colon tissue than normal control. Inhibition of miR-222 expression 
      promoted cell proliferation as well as migration and inhibited autophagy, whereas 
      upregulation of miR-222 had the opposite effect. In addition, miR-222 
      upregulation induced apoptosis and excessive autophagy compared with normal 
      controls (NC). Western blot analysis showed that miR-222 overexpression caused 
      decreased c-kit and SCF protein levels compared with NC. Bioinformatics and 
      luciferase activity analysis revealed that miR-222 could be a predictive 
      regulator of c-kit. CONCLUSION: miR-222 induces apoptosis and excessive autophagy 
      of ICC and may serve as potential biomarker for ICC loss in STC.
FAU - Zheng, Hao
AU  - Zheng H
AD  - Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu Province, China.
FAU - Liu, Yan-Ju
AU  - Liu YJ
AD  - Department of Rehabilitation, Linyi People's Hospital, Linyi, 276003, Shandong 
      Province, China.
FAU - Chen, Zi-Chao
AU  - Chen ZC
AD  - Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 
      250355, Shandong Province, China.
FAU - Fan, Gang-Qi
AU  - Fan GQ
AD  - Department of Cerebropathy, Third Affiliated Hospital of Nanjing University of 
      Chinese Medicine, Nanjing, 210001, Jiangsu Province, China. fgqmed@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210401
PL  - India
TA  - Indian J Gastroenterol
JT  - Indian journal of gastroenterology : official journal of the Indian Society of 
      Gastroenterology
JID - 8409436
RN  - 0 (MIRN222 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - Cell Proliferation
MH  - Constipation/genetics
MH  - *Interstitial Cells of Cajal
MH  - *MicroRNAs/genetics
MH  - Proto-Oncogene Proteins c-kit
MH  - Rats
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Cell counting kit-8 assay
OT  - Gastrointestinal motility disorder
OT  - Interstitial cells of Cajal
OT  - Luciferase reporter assay
OT  - Slow transit constipation
OT  - Stem cell factor
OT  - c-kit
OT  - miR-222
EDAT- 2021/04/02 06:00
MHDA- 2022/01/18 06:00
CRDT- 2021/04/01 12:39
PHST- 2020/10/15 00:00 [received]
PHST- 2020/12/25 00:00 [accepted]
PHST- 2021/04/02 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/04/01 12:39 [entrez]
AID - 10.1007/s12664-020-01143-7 [pii]
AID - 10.1007/s12664-020-01143-7 [doi]
PST - ppublish
SO  - Indian J Gastroenterol. 2021 Apr;40(2):198-208. doi: 10.1007/s12664-020-01143-7. 
      Epub 2021 Apr 1.