miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.

Title

miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.

Creator

Makki Mohammad Shahidul; Haqqi Tariq M

Publisher

Experimental & molecular medicine

Date

2015
2015-10

Description

IL-6 is an inflammatory cytokine and its overexpression plays an important role in osteoarthritis (OA) pathogenesis. Expression of IL-6 is regulated post-transcriptionally by MCPIP1. The 3' untranslated region (UTR) of MCPIP1 mRNA harbors a miR-139 'seed sequence', therefore we examined the post-transcriptional regulation of MCPIP1 by miR-139 and its impact on IL-6 expression in OA chondrocytes. Expression of miR-139 was found to be high in the damaged portion of the OA cartilage compared with unaffected cartilage from the same patient and was also induced by IL-1beta in OA chondrocytes. Inhibition of miR-139 decreased the expression of IL-6 mRNA by 38% and of secreted IL-6 protein by 40%. However, overexpression of miR-139 increased the expression of IL-6 mRNA by 36% and of secreted IL-6 protein by 56%. These data correlated with altered expression profile of MCPIP1 in transfected chondrocytes. Studies with a luciferase reporter construct confirmed the interactions of miR-139 with the 'seed sequence' located in the 3' UTR of MCPIP mRNA. Furthermore, miR-139 overexpression increased the catabolic gene expression but expression of anabolic markers remained unchanged. Overexpression of miR-139 also induced apoptosis in OA chondrocytes. Importantly, we also discovered that IL-6 is a potent inducer of miR-139 expression in OA chondrocytes. These findings indicate that miR-139 functions as a post-transcriptional regulator of MCPIP1 expression and enhances IL-6 expression, which further upregulates miR-139 expression in OA chondrocytes. These results support our hypothesis that miR-139-mediated downregulation of MCPIP1 promotes

Subject

*Apoptosis; 3' Untranslated Regions; Aged; Chondrocytes/*metabolism/pathology; Down-Regulation; Female; Gene Expression Regulation; Humans; Interleukin-6/*genetics; Male; Messenger/genetics; MicroRNAs/*genetics; Middle Aged; Osteoarthritis/*genetics/pathology; Ribonucleases/*genetics; RNA; Transcription Factors/*genetics; Up-Regulation

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

e189–e189

Volume

47

Citation

Makki Mohammad Shahidul; Haqqi Tariq M, “miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.,” NEOMED Bibliography Database, accessed March 7, 2021, https://neomed.omeka.net/items/show/3982.

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