PMID- 31074015 OWN - NLM STAT- MEDLINE DCOM- 20200831 LR - 20200831 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 120 IP - 9 DP - 2019 Sep TI - Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial-mesenchymal transition through targeting miR-342-5p and Wnt3a in anorectal malformations. PG - 15483-15493 LID - 10.1002/jcb.28814 [doi] AB - Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have regulatory functions in varieties of diseases. The purpose of this study was to investigate the potential role of circRNAs in anorectal malformations (ARM). With sequencing analysis, 78 circRNAs were identified to be differentially expressed on gestational day (GD) 19 in ARM and normal anorectal tissues, including 41 upregulated and 37 downregulated circRNAs. Among the downregulated circRNAs, rno_circ_0004002 was selected as the candidate circRNA. Functionally, silencing of rno_circ_0004002 was correlated with suppression of proliferation, and promotion of apoptosis and epithelial-mesenchymal transition (EMT) in anorectal development. For the mechanism investigation, bioinformatic prediction and luciferase reporter assay revealed that rno_circ_0004002 was proved to be a sponge of miR-342-5p, and miR-342-5p could target 3'-UTR of Wnt3a to negatively regulate its expression. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed that the expression of miR-342-5p was significantly increased in ARM anorectal tissues compared with normal tissues on GD19 and GD21, and the expression of Wnt3a demonstrated the opposite on GD21. In addition, rescue assays disclosed that miR-342-5p inhibitor could reverse the role of rno_circ_0004002 knockdown on the repression of anorectal development. In summary, our study shed light on the regulatory mechanism of rno_circ_0004002 in cell proliferation, apoptosis, and EMT via sponging miR-342-5p, which downregulated the Wnt3a expression in anorectal development. We also suggested that GD19 and GD21 was the crucial time in the progression of ARM, and rno_circ_0004002/miR-342-5p/Wnt3a might serve as potential therapeutic targets for ARM. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Qu, Yuan AU - Qu Y AD - Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China. FAU - Liu, Dan AU - Liu D AD - Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China. FAU - Jia, Huimin AU - Jia H AUID- ORCID: 0000-0001-8596-1019 AD - Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China. FAU - Yang, Zhonghua AU - Yang Z AD - Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190509 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (3' Untranslated Regions) RN - 0 (MIRN342 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (WNT3A protein, human) RN - 0 (Wnt3A Protein) SB - IM MH - 3' Untranslated Regions MH - Animals MH - Anorectal Malformations/*genetics MH - Apoptosis MH - Cell Proliferation MH - Cells, Cultured MH - Disease Models, Animal MH - Disease Progression MH - Epithelial-Mesenchymal Transition MH - Gene Expression Regulation MH - HEK293 Cells MH - Humans MH - MicroRNAs/*genetics MH - RNA, Circular/*genetics MH - Rats MH - Sequence Analysis, RNA/*methods MH - Wnt3A Protein/*genetics OTO - NOTNLM OT - Wnt3a OT - anorectal malformations OT - circular RNA OT - epithelial-mesenchymal transition OT - miR-342-5p OT - rno_circ_0004002 EDAT- 2019/05/11 06:00 MHDA- 2020/09/01 06:00 CRDT- 2019/05/11 06:00 PHST- 2019/01/08 00:00 [received] PHST- 2019/02/14 00:00 [revised] PHST- 2019/02/27 00:00 [accepted] PHST- 2019/05/11 06:00 [pubmed] PHST- 2020/09/01 06:00 [medline] PHST- 2019/05/11 06:00 [entrez] AID - 10.1002/jcb.28814 [doi] PST - ppublish SO - J Cell Biochem. 2019 Sep;120(9):15483-15493. doi: 10.1002/jcb.28814. Epub 2019 May 9.