Dysregulation of the miR-34a-SIRT1 axis inhibits breast cancer stemness

// Wei Ma 1, 6 , Gary Guishan Xiao 2, 4 , Jun Mao 1, 3 , Ying Lu 1 , Bo Song 1 , Lihui Wang 1 , Shujun Fan 3 , Panhong Fan 1 , Zhenhuan Hou 1 , Jiazhi Li 1 , Xiaotang Yu 1 , Bo Wang 1 , Huan Wang 3 , Honghai Wang 1 , Fei Xu 6 , Yan Li 6 , Qiang Liu 5 , Lianhong Li 1, 3 1 Department of Pathology, Dalian Medical University, Dalian 116044, China 2 School of Pharmaceutical Sciences, Dalian University of Technology, Dalian 116024, China 3 The Key Laboratory of Tumor Stem Cell Research of Liaoning Province, Dalian Medical University, Dalian 116044, China 4 Genomics and Functional Proteomics Laboratories, Departments of Medicine and Medical Microbiology and Immunology, Creighton University Medical Center, NE 68131, USA 5 Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China 6 Department of Human Anatomy, Dalian Medical University, Dalian 116044, China Correspondence to: Lianhong Li, e-mail: lilianhong917@126.com Gary Guishan Xiao, e-mail: gxiao@dlut.edu.cn Keywords: miR-34α, SIRT1, CD44 + /CD24 − BCSCs, stemness Received: December 16, 2014 Accepted: February 16, 2015 Published: March 18, 2015 ABSTRACT Enforced expression of miR-34a eliminates cancer stem cells in some malignant tumors. Sirtuin-1 (SIRT1) is a direct target of miR-34a. Here we found low levels of miR-34a and high levels of SIRT1 in CD44 + /CD24 − breast cancer stem cells (BCSCs). MiR-34a overexpression and knockdown of SIRT1 decreased proportion of BSCSs and mammosphere formation. Expression of CSC markers, ALDH1, BMI1 and Nanog was decreased. In nude mice xenografts, stable expression of miR-34a and silencing of SIRT1 reduced tumor burden. Taken together, our results demonstrated that miR-34a inhibits proliferative potential of BCSCs in vitro and in vivo , at least partially by downregulating SIRT1. The miR-34a-SIRT1 axis may play role in self-renewal of BCSCs.