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Abstract Number: 2870

Overexpression of EZH2 at the microRNA-142 Regulatory Region Contributes to Down-Regulation of microRNA-142-3p/5p in Systemic Lupus Erythematosus

Shu Ding1, Qing Zhang2, Shuangyan Luo2, Lina Tan1, Hai Long3, Ming Zhao3, Yunsheng Liang2 and Qianjin Lu3, 1Department of Dermatology, The Third Xiangya Hospital of Central South University, Changsha, China, 2Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, China, 3The Second Xiangya Hospital of Central South University, Changsha, China

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Histone Modification, MicroRNA and systemic lupus erythematosus (SLE)

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Session Information

Date: Tuesday, November 15, 2016

Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis - Poster II

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Recently, our group has demonstrated that decreased microRNA-142-3p/5p (miR-142-3p/5p) which contributes to T cell overactivation and B cell hyperstimulation plays an essential role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study is to investigate what regulate miR-142-3p/5p expression in SLE.

Methods:  

CD4+ T cells were isolated from SLE patients and healthy controls. Amounts of H3K27me3, EZH2(H3K27 methyltransferases) within the microRNA-142 (miR-142) regulatory region were subsequently analyzed by chromatin immunoprecipitation (ChIP) and real-time PCR in CD4+ T cells from 20 SLE patients and 20 healthy controls. And miR-142-3p/5p expression levels were determined by real-time quantitative polymerase chain reaction.

Results:

By ChIP and real-time PCR experiments, we confirmed increased H3K27me3 enrichment at the miR-142 regulatory region of SLE CD4+ T cells relative to controls. Moreover, H3K27me3 enrichment at the miR-142 regulatory region was negatively correlated with miR-142-3p/5p expression levels in SLE CD4+ T cells. In addition, a striking increase was observed in EZH2 binding at the miR-142 regulatory region in SLE CD4+ T cells compared to healthy controls. We also proved the levels of EZH2 binding were positively correlated with H3K27me3 enrichment at the miR-142 regulatory region, and negatively correlated with miR-142-3p/5p expression levels. Knocking down EZH2 with siRNA in SLE CD4+ T cells led to decreased EZH2 binding and H3K27me3 enrichment at the miR-142 regulatory region, thus increasing the expression of miR-142-3p/5p.

Conclusion:  

Our findings suggest for the first time that increased EZH2 binding up-regulates H3K27me3 enrichment at the miR-142 regulatory region, which inhibits miR-142-3p/5p expression in SLE CD4+ T cells, and contributes to the development of SLE at last. These results can help elucidate the molecular pathogenesis of SLE, and provide a novel way and target for effective SLE therapy.


Disclosure: S. Ding, None; Q. Zhang, None; S. Luo, None; L. Tan, None; H. Long, None; M. Zhao, None; Y. Liang, None; Q. Lu, None.

To cite this abstract in AMA style:

Ding S, Zhang Q, Luo S, Tan L, Long H, Zhao M, Liang Y, Lu Q. Overexpression of EZH2 at the microRNA-142 Regulatory Region Contributes to Down-Regulation of microRNA-142-3p/5p in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/overexpression-of-ezh2-at-the-microrna-142-regulatory-region-contributes-to-down-regulation-of-microrna-142-3p5p-in-systemic-lupus-erythematosus/. Accessed May 17, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/overexpression-of-ezh2-at-the-microrna-142-regulatory-region-contributes-to-down-regulation-of-microrna-142-3p5p-in-systemic-lupus-erythematosus/

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