PMID- 33506649 OWN - NLM STAT- MEDLINE DCOM- 20211115 LR - 20211115 IS - 1756-185X (Electronic) IS - 1756-1841 (Linking) VI - 24 IP - 3 DP - 2021 Mar TI - MicroRNA-320c inhibits articular chondrocytes proliferation and induces apoptosis by targeting mitogen-activated protein kinase 1 (MAPK1). PG - 402-410 LID - 10.1111/1756-185X.14053 [doi] AB - AIM: To clarify the interaction of microRNA-320c (miR-320c) and mitogen-activated protein kinase 1 (MAPK1), and to investigate the effects of miR-320c on articular chondroctye proliferation and apoptosis. METHODS: Lentiviral expression vectors were constructed and dual luciferase assays containing MAPK1 3'-untranslated regions (3'-UTRs) were performed. Small hairpin RNA (shRNA) was utilized to modulate MAPK1 expression. The messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting respectively. Cell Counting Kit-8 and flow cytometry were conducted to detect the proliferation and apoptosis of Human Chondrocyte-articular (HC-a) cells. Besides that, the influences of miR-320c and MAPK1 on MAPK pathway activation were also evaluated. RESULTS: Our data identified MAPK1 as a direct target gene of miR-320c, and miR-320c can negatively regulate MAPK1 expression by directly binding to MAPK1 3'-UTR in HC-a cells. Further functional study displayed that miR-320c overexpression and MAPK1 shRNA significantly suppressed the proliferation of HC-a cells and promoted cell apoptosis. Meanwhile, MAPK1 shRNA could attenuate miR-320c inhibitor promotive effects on HC-a cell proliferation and reverse its inhibitory effect on cell apoptosis. MAPK1 overexpression could rescue the inhibitory effect of miR-320c on HC-a cell proliferation, and weaken the accelerating effect of miR-320c on cell apoptosis. However, neither miR-320c or MAPK1 shRNA regulate the expression of c-JUN, JNK and c-Fos. CONCLUSION: miR-320c inhibits articular chondrocyte proliferation and induces apoptosis by targeting MAPK1, suggesting that miR-320c perhaps participates in the pathogenesis of osteoarthritis and acts as a potential target for the therapeutic treatment of osteoarthritis. CI - (c) 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd. FAU - Zhao, Like AU - Zhao L AUID- ORCID: 0000-0001-9408-6623 AD - Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhou, Rongwei AU - Zhou R AD - Department of Respiratory and Critical Care Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Wang, Qian AU - Wang Q AD - Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Cheng, Yongjing AU - Cheng Y AD - Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Gao, Ming AU - Gao M AD - Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Huang, Cibo AU - Huang C AD - Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. LA - eng GR - BJ-2018-003/Beijing Hospital Research Foundation/ PT - Journal Article DEP - 20210127 PL - England TA - Int J Rheum Dis JT - International journal of rheumatic diseases JID - 101474930 RN - 0 (MIRN320 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Small Interfering) RN - 9007-49-2 (DNA) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) SB - IM MH - Apoptosis/*genetics MH - Cartilage, Articular/*metabolism/pathology MH - Cell Count MH - Cell Line MH - Cell Proliferation MH - Chondrocytes/metabolism/*pathology MH - DNA/genetics MH - *Gene Expression Regulation MH - Humans MH - MicroRNAs/biosynthesis/*genetics MH - Mitogen-Activated Protein Kinase 1/biosynthesis/*genetics MH - Osteoarthritis/*genetics/metabolism/pathology MH - RNA, Small Interfering/genetics OTO - NOTNLM OT - MAPK1 OT - MiR-320c OT - apoptosis OT - cell proliferation OT - chondrocytes EDAT- 2021/01/29 06:00 MHDA- 2021/11/16 06:00 CRDT- 2021/01/28 05:50 PHST- 2020/09/18 00:00 [received] PHST- 2020/12/09 00:00 [revised] PHST- 2020/12/17 00:00 [accepted] PHST- 2021/01/29 06:00 [pubmed] PHST- 2021/11/16 06:00 [medline] PHST- 2021/01/28 05:50 [entrez] AID - 10.1111/1756-185X.14053 [doi] PST - ppublish SO - Int J Rheum Dis. 2021 Mar;24(3):402-410. doi: 10.1111/1756-185X.14053. Epub 2021 Jan 27.