MiR-23a modulates X-linked inhibitor of apoptosis-mediated autophagy in human luminal breast cancer cell lines
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Ping Chen1,2,*, Yin-Huan He2,*, Xing Huang3,*, Si-Qi Tao2,*, Xiao-Nan Wang2, Hong Yan2, Ke-Shuo Ding2, Peter E. Lobie4,5, Wen-Yong Wu6 and Zheng-Sheng Wu2
1Li Shui People’s Hospital, Nanjing, Jiangsu, China
2Department of Pathology, Anhui Medical University, Hefei, Anhui, China
3Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China
4Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore
5Tsinghua Berkeley Shenzhen Institute, Tsinghua University Graduate School at Shenzhen, Shenzhen, Guangdong, China
6Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
*These authors contributed equally to this work
Zheng-Sheng Wu, email: firstname.lastname@example.org
Wen-Yong Wu, email: email@example.com
Keywords: miR-23a, autophagy, XIAP, breast cancer
Received: April 04, 2017 Accepted: September 03, 2017 Published: September 19, 2017
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 XIAPexpression 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.
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