Down-regulation of miR-543 expression increases the sensitivity of colorectal cancer cells to 5-Fluorouracil through the PTEN/PI3K/AKT pathway.

Abstract:

:Resistance to chemotherapy is one of main obstacles in the treatment of colorectal cancer (CRC). However, the mechanisms are still unclear, and the treatment options are still limited. miR-543 has been indicated to act as an oncogene in some cancers, but its function in regulating chemoresistance has not been considered in CRC cells. This study investigated whether the down-regulation of miR-543 expression enhanced 5-fluorouracil (5-FU)-induced apoptosis in HCT8/FU colon cancer cells. In our study, qRT-PCR revealed that miR-543 expression was up-regulated in the HCT8/FU colon cancer cell line compared with that of HCT8 colon cancer cell line. An miR-543 inhibitor or mimic was transfected, followed by MTT assay to detect 5-FU sensitivity in HCT8 and HCT8/FU cell lines, which showed that IC50 of 5-FU was positively correlated with miR-543 expression. Further studies showed that miR-543 enhanced drug resistance by down-regulating the expression of phosphatase and tensin homolog (PTEN), which negatively regulates protein kinase B (AKT) activation. Additionally, an elevated expression of PTEN reversed the chemoresistance of miR-543-overexpressing HCT8 cells to 5-FU. These results indicate that miR-543 might be a target to increase the sensitivity of CRC cells to 5-FU through the PTEN/PI3K/AKT pathway.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Liu G,Zhou J,Dong M

doi

10.1042/BSR20190249

subject

Has Abstract

pub_date

2019-03-22 00:00:00

issue

3

eissn

0144-8463

issn

1573-4935

pii

BSR20190249

journal_volume

39

pub_type

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