Inhibition of hydrogen sulfide synthesis reverses acquired resistance to 5-FU through miR-215-5p-EREG/TYMS axis in colon cancer cells.

Author(s) Chen, S.; Yue, T.; Huang, Z.; Zhu, J.; Bu, D.; Wang, X.; Pan, Y.; Liu, Y.; Wang, P.
Journal Cancer Lett
Date Published 2019 Dec 01
Abstract

Acquired resistance to 5-fluorouracil (5-FU) is a major barrier to benefit from chemotherapy in colon cancer patients. Hydrogen sulfide (HS), mainly produced by cystathionine-β-synthase (CBS), has been reported to promote the proliferation and migration of colon cancer cells. In this study, the effect of inhibiting HS synthesis on the sensitivity of colon cancer cell lines to 5-FU was investigated. Increased expression of CBS was validated in online database and tissue microarrays. Inhibiting HS synthesis significantly sensitized colon cancer cell lines to 5-FU both in vitro and in vivo. Decreasing HS synthesis utilizing shRNA lentiviruses significantly reversed the acquired resistance to 5-FU. MicroRNA sequencing was performed and miR-215-5p was revealed as one of the miRNAs with most significantly altered expression levels after CBS knock down. Epiregulin (EREG) and thymidylate synthetase (TYMS) were predicted to be potential targets of miR-215-5p. Decreasing HS synthesis significantly decreased the expression of EREG and TYMS. These results demonstrate that inhibiting HS synthesis can reverse the acquired resistance to 5-FU in colon cancer cells.

DOI 10.1016/j.canlet.2019.09.006
ISSN 1872-7980
Citation Chen S, Yue T, Huang Z, Zhu J, Bu D, Wang X, et al. Inhibition of hydrogen sulfide synthesis reverses acquired resistance to 5-FU through miR-215-5p-EREG/TYMS axis in colon cancer cells. Cancer Lett. 2019;466:49-60.

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