CircLRP6调节miR-125a-5p/MCL1轴对 食管鳞癌顺铂耐药性的影响.

Objective To investigate the impacts of circular RNA lipoprotein receptor 6 （circLRP6） on cisplatin （CDDP） resistance to esophageal squamous cell carcinoma （ESCC） and its relevant potential molecular mechanism. Methods CDDP‐resistant cell lines of KYSE30（ KYSE30/CDDP‐R） were established and divided into a control group, si‐NC group, si‐circLRP6 group, si‐circLRP6 plus anti‐NC group, and si‐circLRP6 plus anti‐miR‐ 125a‐5p group. The expression levels of circLRP6, miR‐125a‐5p and myeloid leukemia‐1 （MCL‐1） in tissues/cells were detected by RT‐qPCR and Western blot. CCK‐8 assay was applied to detect the CDDP sensitivity of KYSE30/CDDP‐R cells, so was flow cytometry to detect apoptosis. Results mRNA levels of circLRP6 and MCL‐1 were increased, while level of miR‐125a‐5p was decreased in ESCC cancer tissues/cells and CDDP‐resistant cancer tissues （P < 0.001）. CircLRP6 silencing was able to up‐regulate miR‐125a‐5p, inhibit the expression of MCL‐1, enhance the sensitivity of CDDP‐resistant ESCC cells to CDDP in vitro and in vivo, and promote the apoptosis of CDDP‐resistant ESCC cells. Inhibition of miR‐125a‐5p weakened the effects of circLRP6 silencing on CDDP resistance and apoptosis in CDDP‐resistant ESCC cells （P < 0.05）. circLRP6 could target and negatively regulate the expression of miR‐125a‐5p, and MCL‐1 was the target of miR‐125a‐5p. Conclusion CircLRP6 silencing may enhance the sensitivity of CDDP‐resistant ESCC cells to CDDP through the miR‐125a‐5p/MCL‐1 axis. [ABSTRACT FROM AUTHOR]