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)

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 March 19, 2019.

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