Dichloroacetate restores colorectal cancer chemosensitivity through the p53/miR-149-3p/PDK2-mediated glucose metabolic pathway.

ABSTRACT: The development of chemoresistance remains a major challenge that accounts for colorectal cancer (CRC) lethality. Dichloroacetate (DCA) was originally used as a metabolic regulator in the treatment of metabolic diseases; here, DCA was assayed to identify the mechanisms underlying the chemoresistance of CRC. We found that DCA markedly enhanced chemosensitivity of CRC cells to fluorouracil (5-FU), and reduced the colony formation due to high levels of apoptosis. Using the microarray assay, we noted that miR-149-3p was involved in the chemoresistance of CRC, which was modulated by wild-type p53 after DCA treatment. In addition, PDK2 was identified as a direct target of miR-149-3p. Mechanistic analyses showed that overexpression of miR-149-3p enhanced 5-FU-induced apoptosis and reduced glucose

SUBMITTER: Liang Y 

PROVIDER: S-EPMC6949190 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature