Oncotarget

Research Papers:

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

Wei Lu, Yunping Hu, Qiang Ma, Linzhu Zhou, Lin Jiang, Zhizhen Li, Shuai Zhao, Yuzhen Xu, Weibin Shi, Sheng Li and Yingbin Liu _

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Oncotarget. 2016; 7:62364-62376. https://doi.org/10.18632/oncotarget.11634

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Abstract

Wei Lu1,2,*, Yunping Hu2,*, Qiang Ma2,*, Linzhu Zhou3, Lin Jiang2, Zhizhen Li2, Shuai Zhao2, Yuzhen Xu4, Weibin Shi1, Sheng Li5, Yingbin Liu1,2

1Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China

2Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3Institute of Chemistry, Shanghai Jiao Tong University, Shanghai, China

4Department of Gastrointestinal Surgery, Xu Zhou Center Hospital, Affiliated to Medical College of Southeast University, Jiangsu, China

5Department of Biochemistry, Dalian Medical University, Liaoning, China

*These authors contributed equally to this work

Correspondence to:

Sheng Li, email: [email protected]

Wei Lu, email: [email protected], [email protected]

Yingbin Liu, email: [email protected]

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.


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