Abstract
Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3/LINC00662/miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 193 pathologically diagnosed TNBC patients from 2016 to 2017 in our hospital. Quantitative real-time PCR was used to evaluate the expression of LINC00662 and miR-186-5p both in vivo and in vitro. CCK8 tests were used to assess cell viability. ELISA was used for protein expression evaluation. Dual luciferase reporter gene assay and RNA pull-down were used to evaluate the interaction between LINC00662 and miR-186-5p. m6A levels were enhanced in breast cancer tissues and cells. LINC00662, miR-186-5p and METTL3 were differentially expressed in vivo, and METTL3 expression was associated with LINC00662 and miR-186-5p expression. LINC00662 and miR-186-5p were differentially expressed in vitro; LINC00662 promoted cell viability and decreased the apoptosis rate, whereas miR-186-5p inhibited cell viability and increased the apoptosis rate. Furthermore, we found that METTL3 regulated m6A levels in docetaxel-resistant breast cancer cells by regulating the expression of LINC00662. Moreover, LINC00662 and miR-186-5p regulated the cell viability rate of docetaxel-resistant breast cancer cells. Further experiments showed that LINC00662 directly interacted with miR-186-5p to exert biological functions; besides miR-186-5p could regulate the expression of METTL3. METTL3 promotes m6A levels and docetaxel resistance in breast cancer by regulating the expression of LINC00662 and miR-186-5p; more experiments are needed to clarify the role of m6A regulation in drug resistance.