PMID- 32244197
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 127
DP  - 2020 Jul
TI  - Upregulation of miR-92a-2-5p potentially contribute to anorectal malformations by 
      inhibiting proliferation and enhancing apoptosis via PRKCA/beta-catenin.
PG  - 110117
LID - S0753-3322(20)30309-7 [pii]
LID - 10.1016/j.biopha.2020.110117 [doi]
AB  - Anorectal malformations (ARMs) is one of the most common gastrointestinal 
      anomalies. Previous research revealed that miR-92a-2-5p was upregulated in ARMs. 
      However, the underlying roles remains unknown. The current study was to further 
      investigate the spatiotemporal expression patterns of miR-92a-2-5p and its target 
      gene protein kinase C alpha (PRKCA) predicted by bioinformatic method, and to 
      explore their potential functions in anorectal malformations (ARMs). Rat models 
      with ethylenethiourea-induced ARMs were made for subsequent experiments. Direct 
      target relationship between miR-92a-2-5p and PRKCA was validated using a 
      luciferase reporter assay. The spatiotemporal expression pattern of miR-92a-2-5p 
      was evaluated using fluorescence in situ hybridization (FISH), while the 
      expression of PRKCA was revealed by immunohistochemical staining and western 
      blotting. IEC-6 cells were transfected with mimics/mimics NC (Negative 
      control)/inhibitor/inhibitor NC of miR-92a-2-5p or si-PRKCA/si-PRKCA NC, 
      respectively. Then the downstream molecules of miR-92a-2-5p, PRKCA and beta-catenin, 
      were subsequently detected. Meanwhile, apoptosis and viability assays were 
      measured. Dual luciferase assay confirmed the direct regulatory relationship 
      between miR-92a-2-5p and PRKCA. FISH revealed that miR-92a-2-5p was expressed 
      with a higher level in ARMs fetuses. Further analyses of PRKCA showed lower 
      protein expression level in ARMs group, which was opposite to miR-92a-2-5p. In 
      vitro experiments revealed that overexpression of miR-92a-2-5p or knockdown of 
      PRKCA can down-regulate PRKCA, up-regulate and facilitate nuclear localization of 
      beta-catenin, increase apoptosis and decrease proliferation of IEC-6. Taken 
      together, these findings suggest that aberrantly high expression of miR-92a-2-5p 
      potentially contribute to ARMs by inhibiting proliferation and enhancing 
      apoptosis of intestinal cells via negatively regulating PRKCA/beta-catenin.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Long, Cai Yun
AU  - Long CY
AD  - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, 110004, PR China.
FAU - Xiao, Yun Xia
AU  - Xiao YX
AD  - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, 110004, PR China.
FAU - Li, Si Ying
AU  - Li SY
AD  - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, 110004, PR China.
FAU - Tang, Xiao Bing
AU  - Tang XB
AD  - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, 110004, PR China.
FAU - Yuan, Zheng Wei
AU  - Yuan ZW
AD  - The Key Laboratory of Health Ministry for Congenital Malformation, Shengjing 
      Hospital of China Medical University, Shenyang, Liaoning, 110004, PR China.
FAU - Bai, Yu Zuo
AU  - Bai YZ
AD  - Department of Pediatric Surgery, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, 110004, PR China. Electronic address: baiyz1216@126.com.
LA  - eng
PT  - Journal Article
DEP - 20200331
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (MIRN92 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (beta Catenin)
RN  - 24FOJ4N18S (Ethylenethiourea)
RN  - EC 2.7.11.13 (Protein Kinase C-alpha)
SB  - IM
MH  - Animals
MH  - Anorectal Malformations/chemically induced/*physiopathology
MH  - Apoptosis/*physiology
MH  - Cell Proliferation/*physiology
MH  - Ethylenethiourea
MH  - Female
MH  - MicroRNAs/biosynthesis/*physiology
MH  - Protein Kinase C-alpha/biosynthesis
MH  - Rats
MH  - Up-Regulation
MH  - beta Catenin/*biosynthesis
OTO - NOTNLM
OT  - Anorectal malformation
OT  - Apoptosis
OT  - Development
OT  - Proliferation
OT  - Spatiotemporal expression
COIS- Declaration of competing Interest The authors declares that they have no 
      competing interests.
EDAT- 2020/04/04 06:00
MHDA- 2021/02/17 06:00
CRDT- 2020/04/04 06:00
PHST- 2020/01/04 00:00 [received]
PHST- 2020/03/17 00:00 [revised]
PHST- 2020/03/19 00:00 [accepted]
PHST- 2020/04/04 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/04/04 06:00 [entrez]
AID - S0753-3322(20)30309-7 [pii]
AID - 10.1016/j.biopha.2020.110117 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2020 Jul;127:110117. doi: 10.1016/j.biopha.2020.110117. Epub 
      2020 Mar 31.