MiR-26b Regulates 5-FU-resistance in Human Colorectal Cancer Via Down-regulation of Pgp

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2019 Jan 22

PMID 30662808

Citations 26

Authors

Bin Wang

Fen-Ying Lu

Rui-Hua Shi

Ya-Dong Feng

Xiao-Dan Zhao

Zhi-Ping Lu

Long Xiao

Guo-Qiang Zhou

Jia-Ming Qiu

Cui-E Cheng

Affiliations

Soon will be listed here.

Abstract

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU and enhanced the potency of 5-FU in the inhibition of tumor growth . We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.

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