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Tumor Biology
Published in: Tumor Biology 9/2016

01-09-2016 | Original Article

Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2)

Authors: Yingyi Liu, Sujie Gao, Xuebo Chen, Meihan Liu, Cuiying Mao, Xuedong Fang

Published in: Tumor Biology | Issue 9/2016

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Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression through the endogenous RNA interference machinery. Treatments with combination of chemotherapy with surgery are essential for advanced-stage colorectal cancer. However, the development of chemoresistance is a major obstacle for clinical application of anticancer drugs. In this study, we report a miR-203-SIK2 axis that involves in the regulation of Taxol sensitivity in colon cancer cells. MiR-203 is downregulated in human colon tumor specimens and cell lines compared with their normal counterparts. We report miR-203 is correlated with Taxol sensitivity: overexpression of miR-203 sensitizes colon cancer cells and the Taxol-resistant cells display downregulated miR-203 compared with Taxol-sensitive cells. We identify SIK2 as a direct target of miR-203 in colorectal cancer cells. Overexpression of miR-203 complementary pairs to the 3′ untranslated region (UTR) of SIK2, leading to the sensitization of Taxol resistant cells. In addition, miR-203 and the salt-inducible kinase 2 (SIK2) are reverse expressed in human colorectal tumors. Finally, we demonstrate recovery of SIK2 by overexpression of SIK2-desensitized Taxol-resistant cells, supporting the miR-203-mediated sensitization to Taxol, is through the inhibition of SIK2. In general, our study will provide mechanisms of the microRNA-based anti-tumor therapy to develop anti-chemoresistance drugs.
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Metadata
Title
Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2)
Authors
Yingyi Liu
Sujie Gao
Xuebo Chen
Meihan Liu
Cuiying Mao
Xuedong Fang
Publication date
01-09-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5066-2

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