title: miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1.
abstract: BACKGROUND
  MicroRNAs (miRs) are involved in cancer carcinogenesis, and certain regulatory miRs could provide promising therapeutic methods for refractory malignancies, such as gallbladder cancer (GBC). miR-223 was found to play a pivotal role in enhancing chemotherapeutic effects, therefore evoking interest in the role of miR-223 in GBC.
  
  
  RESULTS
  miR-223 was decreased in GBC tissues and cell lines, and ectopic miR- 223 expression exhibited multiple anti-tumorigenic effects in GBC cells, including decreased proliferation, migration and invasion in vitro. However, treatment with a miR-223 inhibitor increased cell viability. We determined that STMN1 was negatively correlated with and regulated by miR-223 in GBC. miR-223 increased GBC sensitivity to docetaxel in vitro and in vivo, and the induced sensitivity to docetaxel was suppressed by the restoration of STMN1 expression.
  
  
  METHODS
  We examined miR-223 expression in GBC tissue and GBC cell lines using qRT-PCR. The effects of modulated miR-223 expression in GBC cells were assayed using Cell Counting Kit-8 (CCK8), flow cytometry, and wound-healing and invasion assays. Susceptibility to docetaxel was evaluated in miR-223/STMN1-modulated GBC cells and xenograft tumor models. The protein expression of relevant genes was examined by Western blotting.
  
  
  CONCLUSIONS
  These findings indicated that miR-223 might serve as an onco-suppressor that enhances susceptibility to docetaxel by downregulating STMN1 in GBC, highlighting its promising therapeutic value.
authors: Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Wei
authors: W
authors: Lu
authors: Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yunping
authors: Y
authors: Hu
authors: Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Qiang
authors: Q
authors: Ma
authors: Institute of Chemistry, Shanghai Jiao Tong University, Shanghai, China.
authors: Linzhu
authors: L
authors: Zhou
authors: Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Lin
authors: L
authors: Jiang
authors: Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zhizhen
authors: Z
authors: Li
authors: Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Shuai
authors: S
authors: Zhao
authors: Department of Gastrointestinal Surgery, Xu Zhou Center Hospital, Affiliated to Medical College of Southeast University, Jiangsu, China.
authors: Yuzhen
authors: Y
authors: Xu
authors: Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
authors: Weibin
authors: W
authors: Shi
authors: Department of Biochemistry, Dalian Medical University, Liaoning, China.
authors: Sheng
authors: S
authors: Li
authors: Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.|Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Yingbin
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D000077143:Docetaxel; D015536:Down-Regulation; D005434:Flow Cytometry; D005704:Gallbladder / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D035683:MicroRNAs; D050777:Stathmin; D043823:Taxoids; C525067:MIR223, human; C493995:STMN1 protein, human
keywords: STMN1; gallbladder cancer; malignancy; miR-223