The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus.

Abstract

BACKGROUND:

The pathogenesis of systemic lupus erythematosus (SLE) has not yet been completely elucidated. One of the hallmarks of SLE is the production of autoantibodies by uncontrolled over-activated B cells. Early B cell factor 1 (EBF1) contributes to the development, activation, and proliferation of B cells through activation of the AKT signaling pathway. Accumulating evidence has demonstrated that several microRNAs (miRNAs) contribute to the pathogenesis of autoimmune diseases through the regulation of B cells in SLE. We aim to investigate the expression patterns of miR-1246 in B cells and its contribution to pathogenesis of SLE.

RESULTS:

Our results showed that the expression of miR-1246 was significantly decreased in B cells from SLE patients. We verified that miR-1246 specifically targeted the EBF1 messenger RNA (mRNA) by interacting with its 3'-untranslated region (3'-UTR) and regulated the expression of EBF1. Transfection of miR-1246 inhibitors into healthy B cells upregulated the expression of EBF1, enhanced B cell function, and increased the production of B cell surface co-stimulatory molecules CD40, CD80, and CD86. We also observed that abnormal activation of the AKT signaling pathway was associated with decreased P53 expression, leading to the downregulation of the miR-1246 expression; and upregulation of the miR-1246 expression reversed the responsiveness of B cells by inhibiting EBF1 expression.

CONCLUSIONS:

Activated B cells in lupus could decrease the expression of miR-1246 through the AKT-P53 signaling pathway, which in turn enhances the expression of EBF1, thereby promoting further activation of B cells. Conversely, upregulation of miR-1246 could interrupt this amplification pathway. Our findings thus provide a theoretical framework towards the research of novel biological targets in SLE treatment.

• Authors: Shuangyan Luo, Yu Liu, Gongping Liang, Ming Zhao, Haijing Wu, Yunsheng Liang, Xiangning Qiu, Yixin Tan, Yong Dai, Susan Yung, Tak-Mao Chan, Qianjin Lu
• Journal: Clinical epigenetics (Clin Epigenetics) Vol. 7 Pg. 24 ( 2015) ISSN: 1868-7075 [Print] Germany
• PMID: 25789080 (Publication Type: Journal Article)