title: 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: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Shuangyan
authors: S
authors: Luo
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Yu
authors: Y
authors: Liu
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Gongping
authors: G
authors: Liang
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Ming
authors: M
authors: Zhao
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Haijing
authors: H
authors: Wu
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Yunsheng
authors: Y
authors: Liang
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Xiangning
authors: X
authors: Qiu
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Yixin
authors: Y
authors: Tan
authors: Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020 People's Republic of China.
authors: Yong
authors: Y
authors: Dai
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, 999077 China.
authors: Susan
authors: S
authors: Yung
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, 999077 China.
authors: Tak-Mao
authors: TM
authors: Chan
authors: Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan 410011 China.
authors: Qianjin
authors: Q
authors: Lu
keywords: AKT; B cell; Co-stimulatory molecules; EBF1; Has-miR-1246; P53; Systemic lupus erythematosus