miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1

// Wei Lu 1, 2, * , Yunping Hu 2, * , Qiang Ma 2, * , Linzhu Zhou 3 , Lin Jiang 2 , Zhizhen Li 2 , Shuai Zhao 2 , Yuzhen Xu 4 , Weibin Shi 1 , Sheng Li 5 , Yingbin Liu 1, 2 1 Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China 2 Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China 3 Institute of Chemistry, Shanghai Jiao Tong University, Shanghai, China 4 Department of Gastrointestinal Surgery, Xu Zhou Center Hospital, Affiliated to Medical College of Southeast University, Jiangsu, China 5 Department of Biochemistry, Dalian Medical University, Liaoning, China * These authors contributed equally to this work Correspondence to: Sheng Li, email: lisheng@dmu.edu.cn Wei Lu, email: wellu@163.com , wellu@sjtu.edu.cn Yingbin Liu, email: liuybphd@126.com Keywords: miR-223, gallbladder cancer, malignancy, STMN1 Received: January 25, 2016      Accepted: August 23, 2016      Published: August 26, 2016 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.