MiR-153 inhibits the resistance of lung cancer to gefitinib via modulating expression of ABCE1.

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MiR-153 inhibits the resistance of lung cancer to gefitinib via modulating expression of ABCE1.

Cancer Biomark. 2019 Jun 28;:

Authors: Wang L, Lv X, Fu X, Su L, Yang T, Xu P

Abstract
BACKGROUND: Gefitinib-resistance in lung cancers has become an intractable clinical problem. However, the mechanisms underlying this resistance are not fully understood.
OBJECTIVE: Present study aims to investigate the roles and underlying mechanism of miR-153 in modulating gefitinib resistance in lung cancers.
METHODS: In the present study, genes expression of miR-153, MDR-1 and ABCE1 were detected by qRT-PCR and western blot. The cell viability was examined by MTT assays. The regulation of miR-153 on ABCE1 was examined by luciferase reporter gene assays. The interaction of miR-153 and ABCE1 was detected by gene over-expression and siRNA interference technology.
RESULTS: The mRNA level of miR-153 was significantly down-regulated in gefitinib-resistance (GR) tissues and HCC827 cells, while the protein level of ABCE1 was up-regulated in GR tissues and HCC827 cells. Besides, miR-153 over-expression evidently increased miR-153 level and suppressed cell viability and multi drug resistance gene (MDR-1) expression in HCC827/Gef cells, while silence of miR-153 caused adverse alterations in HCC827 cells. Luciferase reporter assay results showed that miR-153 directly targeted ABCE1. Further studies showed that ABCE1 over-expression improved the expression of ABCE1 and MDR-1 and increased cell viability in HCC827/Gef cells, while ABCE1 silencing resulted in contrary trends in HCC827 cells. What's more, miR-153 over-expression inhibited tumorigenesis and ABCE1 expression, while increased miR-153 level in tumor tissues.
CONCLUSIONS: MiR-153 regulates gefitinib resistance by modulating expression of ABCE1 in lung cancers. Our findings may provide a worthwhile therapeutic target to reverse gefitinib resistance in lung cancers in the future.

PMID: 31306106 [PubMed - as supplied by publisher]