title: SOX2 regulates multiple malignant processes of breast cancer development through the SOX2/miR-181a-5p, miR-30e-5p/TUSC3 axis.
abstract: High levels of SOX2 protein are correlated with increased dissemination of breast cancer. However, the underlying molecular mechanisms are not fully understood.
  
  
  
  In this study we investigate the role of SOX2 in breast cancer metastasis using multiple in vitro and in vivo assays including cell culture, shRNA-mediated knockdown, wound healing, colony formation, transwell chamber, xenograft and tail vein injection. Moreover, western blot, immunostaining, microarray and real-time PCR were used to determine the change of protein and miRNA levels. Luciferase assays were also used to evaluate activity which TUSC3 is a target of miR-181a-5p and miR-30e-5p, and the clinical survival relevance was analyzed by Kaplan-Meier analysis.
  
  
  
  We identified a novel pathway involving SOX2 regulation of microRNAs to control the proliferation and migration of breast cancer cells. shRNA-mediated knockdown of SOX2 inhibits breast cancer cell expansion and migration. More importantly, we found that these changes are accompanied by significant reduction in the levels of two microRNAs, miR-181a-5p and miR-30e-5p. Overexpression of these two microRNAs leads to reduced protein levels of Tumor Suppressor Candidate 3 (TUSC3) in breast cancer cells; mutations of the potential binding sites in the 3'-UTR of TUSC3 abrogate the inhibitory effects of the microRNAs. We further found that upregulation of TUSC3 expression leads to reduced proliferation and migration of breast cancer cells. In human breast cancer samples the levels of TUSC3 protein are inversely correlated with those of SOX2 protein.
  
  
  
  Taken together, our work reveals a novel SOX2-mediated regulatory axis that plays critical roles in the proliferation, migration and invasiveness of breast cancer cells. Targeting this axis may provide beneficial effect in the treatment of breast cancer.
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China. Liukuancan@163.com.|Department of Medicine, Columbia University Medical Center, New York, 10032, NY, USA. Liukuancan@163.com.|Dong fang Hospital, Xiamen University, Fuzhou, 350025, Fujian, People's Republic of China. Liukuancan@163.com.|Fuzhou General Hospital Clinical Medical School, Fujian Medical University, Fuzhou, 350025, People's Republic of China. Liukuancan@163.com.
authors.forename: Kuancan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China.|Dong fang Hospital, Xiamen University, Fuzhou, 350025, Fujian, People's Republic of China.
authors.forename: Fuan
authors.initials: F
authors.lastname: Xie
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China.|Dong fang Hospital, Xiamen University, Fuzhou, 350025, Fujian, People's Republic of China.
authors.forename: Anding
authors.initials: A
authors.lastname: Gao
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China.|Fuzhou General Hospital Clinical Medical School, Fujian Medical University, Fuzhou, 350025, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Life Science Institute, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Emergency Department of the 476 Hospital, Fuzhou General Hospital, PLA, Fuzhou, 350002, Fujian, People's Republic of China.
authors.forename: Zhangwu
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Dong fang Hospital, Xiamen University, Fuzhou, 350025, Fujian, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Medical College, China Three Gorges University, Yichang, 443002, Hubei, People's Republic of China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China.
authors.forename: Qiaojia
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China.|Dong fang Hospital, Xiamen University, Fuzhou, 350025, Fujian, People's Republic of China.
authors.forename: Baoshun
authors.initials: B
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, 14642, NY, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, People's Republic of China.
authors.forename: Haikun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, 10032, NY, USA. jq2240@cumc.columbia.edu.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Que
authors.affiliation: Institute for Laboratory Medicine, Fuzhou General Hospital, PLA, Fuzhou, 350025, Fujian, People's Republic of China. Lanxp@sina.com.|Fuzhou General Hospital Clinical Medical School, Fujian Medical University, Fuzhou, 350025, People's Republic of China. Lanxp@sina.com.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Lan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008954:Models, Biological; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D055748:SOXB1 Transcription Factors / Q000235:genetics*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000608460:MIRN-181 microRNA, human; C546086:MIRN30b microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins
keywords: Breast cancer; Sox2; Tumourigenesis; miRNA