MiR-23a modulates X-linked inhibitor of apoptosis -mediated autophagy in human luminal breast cancer cell lines

// Ping Chen 1, 2, * , Yin-Huan He 2, * , Xing Huang 3, * , Si-Qi Tao 2, * , Xiao-Nan Wang 2 , Hong Yan 2 , Ke-Shuo Ding 2 , Peter E. Lobie 4, 5 , Wen-Yong Wu 6 and Zheng-Sheng Wu 2 1 Li Shui People’s Hospital, Nanjing, Jiangsu, China 2 Department of Pathology, Anhui Medical University, Hefei, Anhui, China 3 Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China 4 Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore 5 Tsinghua Berkeley Shenzhen Institute, Tsinghua University Graduate School at Shenzhen, Shenzhen, Guangdong, China 6 Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China * These authors contributed equally to this work Correspondence to: Zheng-Sheng Wu, email: woozson@yahoo.com Wen-Yong Wu, email: ayfywwy@sina.cn Keywords: miR-23a, autophagy, XIAP, breast cancer Received: April 04, 2017      Accepted: September 03, 2017      Published: September 19, 2017 ABSTRACT Autophagy is a conserved multi-step lysosomal process that is induced by diverse stimuli including cellular nutrient deficiency. X-linked inhibitor of apoptosis ( XIAP ) promotes cell survival and recently has been demonstrated to suppress autophagy. Herein, we examined regulation of XIAP -mediated autophagy in breast cancer cells and determined the underlying molecular mechanism. To investigate this process, autophagy of breast cancer cells was induced by Earle’s balanced salt solution (EBSS). We observed discordant expression of XIAP mRNA and protein in the autophagic process induced by EBSS, suggesting XIAP may be regulated at a post-transcriptional level. By scanning several miRNAs potentially targeting XIAP , we observed that forced expression of miR-23a significantly decreased the expression of XIAP and promoted autophagy, wherever down-regulation of miR-23a increased XIAP expression and suppressed autophagy in breast cancer cells. XIAP was confirmed as a direct target of miR-23a by reporter assay utilizing the 3’UTR of XIAP . In vitro , forced expression of miR-23a promoted autophagy, colony formation, migration and invasion of breast cancer cell by down-regulation of XIAP expression. However, miR-23a inhibited apoptosis of breast cancer cells independent of XIAP . Xenograft models confirmed the effect of miR-23a on expression of XIAP and LC3 and that miR-23a promoted breast cancer cell invasiveness. Therefore, our study demonstrates that miR-23a modulates XIAP -mediated autophagy and promotes survival and migration in breast cancer cells and hence provides important new insights into the understanding of the development and progression of breast cancer.