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Acta Biochim Biophys Sin (Shanghai). 2018 Jun 1;50(6):597-604. doi: 10.1093/abbs/gmy040.

MiR-223 promotes the doxorubicin resistance of colorectal cancer cells via regulating epithelial-mesenchymal transition by targeting FBXW7.

Author information

1
Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
2
Department of Physiology, School of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, China.
3
Department of Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China.
4
Department of Pharmaceutics, School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China.
5
Department of Medical Ultrasound, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, China.

Abstract

Although doxorubicin has become a key drug in cancer treatment, the resistance of colorectal carcinoma to doxorubicin is a major problem in clinical practice. F-box and WD repeat domain-containing 7 (FBXW7) plays important roles in human cancers and is one of the major causes of drug resistance. The miR-223/FBXW7 pathway has been reported to be a crucial clue to the mechanism of chemoresistance in many human cancers, such as gastric cancer, breast cancer, and non-small cell lung cancer. However, it is unclear whether similar mechanisms of doxorubicin resistance are involved in colorectal cancer (CRC). The aim of the current study was to evaluate the role of miR-223/FBXW7 pathway in chemosensitivity in different CRC cell lines and to investigate the relevant underlying mechanisms. We found that high levels of FBXW7 expression were associated with increased doxorubicin sensitivity in different CRC cell lines, and FBXW7 was regulated by miR-223. Overexpression of miR-223 decreased FBXW7 expression and the sensitivity of CRC cells to doxorubicin, while suppression of miR-223 had the opposite effect. Moreover, epithelial-mesenchymal transition (EMT) was proved to be regulated by miR-223/FBXW7 pathway and involved in the drug resistance. In conclusion, miR-223/FBXW7 axis regulates doxorubicin sensitivity through EMT in CRC, which may lead to the development of individualized treatment in clinical practice.

PMID:
29701752
DOI:
10.1093/abbs/gmy040
[Indexed for MEDLINE]

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