Oncotarget

Research Papers:

miR-106b regulates the 5-fluorouracil resistance by targeting Zbtb7a in cholangiocarcinoma

Dechao Jiao, Yan Yan, Shaofeng Shui, Gang Wu, JianZhuang Ren, Yanli Wang and Xinwei Han _

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Oncotarget. 2017; 8:52913-52922. https://doi.org/10.18632/oncotarget.17577

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Abstract

Dechao Jiao1, Yan Yan2, Shaofeng Shui3, Gang Wu3, JianZhuang Ren3, Yanli Wang3 and Xinwei Han3

1Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China

2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China

3Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China

Correspondence to:

Xinwei Han, email: rug025@163.com

Keywords: MicroRNA-106b, chemoresistance, cholangiocarcinoma, 5-fluorouracil, Zbtb7a

Received: January 12, 2017    Accepted: February 12, 2017    Published: May 02, 2017

ABSTRACT

Background: Cholangiocarcinoma (CCA) is highly resistant to chemo-therapy, including 5-fluorouracil (5-FU) treatment. MicroRNAs are endogenous and short non-coding RNAs that can regulate multiple genes expression. Many microRNAs have shown functional roles in the chemo-resistance of tumors. Here, we examined the relationship between microRNAs expression and the sensitivity of CCA cells to 5-FU.

Methods: Microarray analysis was used to determine the aberrantly expressed microRNAs in two 5-FU resistant CCA cell lines, KKU-M139 and KKU-M214 cells. To determine the effect of candidate microRNAs on 5-FU sensitivity, expression of candidate was modified via either transfection of a microRNA mimic or transfection of an antagonist. Ontology-based programs were also used to investigate the potential targets of microRNAs that were confirmed to affect the 5-FU sensitivity of CCA cells.

Results: The microRNA-106b (miR-106b) was significantly down-regulated in 5-FU resistant CCA cells. Instead, over-expression of miR-106b could re-sensitize resistant CCA cells to 5-FU through down-regulation of Zbtb7a. Moreover, decreased expression of miR-106b is related to poor prognosis in patients with CCA, suggesting its potential role as a new prognostic marker in CCA.

Conclusion: Our study demonstrates that miR-106b can reverse 5-FU resistance via Zbtb7a suppression, thus offer a novel and powerful strategy for CCA chemotherapy.


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