PMID- 34804121 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211123 IS - 1664-8021 (Print) IS - 1664-8021 (Electronic) IS - 1664-8021 (Linking) VI - 12 DP - 2021 TI - Hsa_circRNA_103124 Upregulation in Crohn's Disease Promotes Cell Proliferation and Inhibits Autophagy by Regulating the Hsa-miR-650/AKT2 Signaling Pathway. PG - 753161 LID - 10.3389/fgene.2021.753161 [doi] LID - 753161 AB - Circular RNAs (circRNAs) play important roles in the pathogenesis of Crohn's disease (CD). We discovered that hsa_circRNA_103124 was upregulated in CD patients in our previous study. Nonetheless, the function of hsa_circRNA_103124 is unclear. In this study, hsa_circRNA_103124 was predicted to interact with hsa-miR-650. Gene Ontology (GO) and pathway analyses identified AKT serine/threonine kinase 2 (AKT2) as the downstream target protein of hsa-miR-650. Activated AKT2 inhibits autophagy, but promotes cell proliferation. Recent studies suggest that the inhibition of autophagy is one of the mechanisms of CD pathogenesis. Therefore, we inferred that hsa_circRNA_103124 might regulate autophagy and proliferation by targeting AKT2 as a sponge for hsa-miR-650. Here, quantitative reverse transcription PCR (RT-QPCR) results revealed that upregulated hsa_circRNA_103124 expression in patients with CD was negatively correlated with hsa-miR-650 expression but positively correlated with the white blood cell count and calprotectin levels. TSC complex subunit 1 (TSC1), one of the proteins upstream of autophagy was downregulated in patients with CD. Consisting with the bioinformatics prediction, it was verified that hsa_circRNA_103124 targeted to hsa-miR650 by fluorescence in situ hybridization (FISH) and luciferase reporter assays. A hsa-miR-650 inhibitor reversed the promotion of rapamycin-induced autophagy and the inhibition of cell proliferation by the hsa_circRNA_103124 siRNA. However, hsa-miR-650 mimics reversed the inhibition of rapamycin-induced autophagy and the promotion of cell proliferation through hsa_circRNA_103124 overexpression. These results indicate that hsa_circRNA_103124 upregulation in patients with CD promotes cell proliferation and inhibits autophagy by regulating the hsa-miR-650/AKT2 signaling pathway. CI - Copyright (c) 2021 Yin, Tong, Ye, Hu, Xu, Zhang, Zhu and Pang. FAU - Yin, Juan AU - Yin J AD - Department of Digestive Disease and Nutrition Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Tong, Fuyi AU - Tong F AD - The Fifth People's Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China. FAU - Ye, Yulan AU - Ye Y AD - Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Hu, Tong AU - Hu T AD - Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Xu, Lijuan AU - Xu L AD - Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Zhang, Liping AU - Zhang L AD - Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Zhu, Jianyun AU - Zhu J AD - Department of Digestive Disease and Nutrition Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. FAU - Pang, Zhi AU - Pang Z AD - Department of Digestive Disease and Nutrition Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. AD - Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China. LA - eng PT - Journal Article DEP - 20211105 PL - Switzerland TA - Front Genet JT - Frontiers in genetics JID - 101560621 PMC - PMC8602894 OTO - NOTNLM OT - AKT2 OT - Cohn's disease OT - autophagy OT - hsa-miR-650 OT - hsa_circRNA_103124 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/11/23 06:00 MHDA- 2021/11/23 06:01 PMCR- 2021/11/05 CRDT- 2021/11/22 06:41 PHST- 2021/08/04 00:00 [received] PHST- 2021/10/20 00:00 [accepted] PHST- 2021/11/22 06:41 [entrez] PHST- 2021/11/23 06:00 [pubmed] PHST- 2021/11/23 06:01 [medline] PHST- 2021/11/05 00:00 [pmc-release] AID - 753161 [pii] AID - 10.3389/fgene.2021.753161 [doi] PST - epublish SO - Front Genet. 2021 Nov 5;12:753161. doi: 10.3389/fgene.2021.753161. eCollection 2021.