Dysregulation of the BRCA1/long non-coding RNA NEAT1 signaling axis contributes to breast tumorigenesis

• DOI: 10.18632/oncotarget.11364
• Publication Date: 2016-08-18T16:56:45Z
• Authors: Pang-Kuo Lo; Yongshu Zhang; Benjamin Wolfson; Ramkishore Gernapudi; Yuan Yao; Nadire Duru; Qun Zhou
• Keywords: Mice, Knockout; 0301 basic medicine; BRCA1 Protein; Breast Neoplasms; 3. Good health; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Mice; MicroRNAs; 03 medical and health sciences; Cell Transformation, Neoplastic; Wnt4 Protein; Animals; Humans; Female; RNA, Long Noncoding; Research Paper; Signal Transduction

// Pang-Kuo Lo 1 , Yongshu Zhang Benjamin Wolfson Ramkishore Gernapudi Yuan Yao Nadire Duru Qun Zhou Department of Biochemistry and Molecular Biology, Greenebaum Cancer Center, University Maryland School Medicine, Baltimore, MD 21201, USA Correspondence to: Zhou, email: [e-mail] Keywords: BRCA1, NEAT1, miR-129, WNT4, breast cancer stem cells Received: March 18, 2016      Accepted: August 10, Published: 2016 ABSTRACT Dysregulation long non-codng RNA (lncRNA) expression has been found to contribute tumorigenesis. However, the roles lncRNAs in BRCA1-related remain largely unknown. In this study, we delineate role novel BRCA1/lncRNA NEAT1 signaling axis BRCA1 inhibits potentially through binding its genomic site upstream gene. deficiency human normal/cancerous mouse mammary glands leads overexpression. Our studies show that upregulation resulting from stimulates vitro vivo tumorigenicity. We have further identified molecular mediators downstream BRCA1/NEAT1 axis. epigenetically silences miR-129-5p by promoting DNA methylation CpG island miR-129 Silencing results WNT4 expression, a target miR-129-5p, which activation oncogenic WNT signaling. functional indicate NEAT1/miR-129-5p/WNT4 contributes tumorigenic effects deficiency. Finally our silico correlation analysis suggests existence BRCA1/NEAT1/miR-129-5p cancer. findings, taken together, suggest dysregulation BRCA1/NEAT1/miR-129-5p/WNT4 is involved