Effect of miR-133b on progression and cisplatin resistance of triple-negative breast cancer through FGFR1-Wnt-β-catenin axis

Am J Transl Res. 2021 Jun 15;13(6):5969-5984. eCollection 2021.


Background: As a type of breast cancer that has relatively strong invasiveness, triple negative breast cancer (TNBC) seriously affects the survival of patients. microRNAs (miRNAs) have been shown to exert a prominent regulatory effect on the disease, among which miR-133b is reported to be involved in the pathological mechanism of breast cancer, but its role in TNBC remains unclear.

Methods: In this study, real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were performed for detecting the expressions of miR-133b, fibroblast growth factor receptor 1 (FGFR1), and Wingless/Integrated (Wnt)-β-catenin pathway markers (Wnt1, β-catenin, nuclear-β-catenin, p-GSK-3β, GSK-3β, cyclinD1, and FOXQ1). With TNBC cells and DDP-resistant TNBC cells (TNBC/DDP cells) used as research objects, their proliferation and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assays and Flow cytometry, respectively. Then, the targeted relationship between miR-133b and FGFR1 was verified by Dual luciferase reporter gene assay (DLRGA).

Results: In our study, miR-133b was down-regulated while FGFR1 up-regulated in TNBC. The ectopic expression of miR-133b remarkably inhibited the proliferation and colony formation but induced apoptosis of TNBC cells, and inactivated the Wnt-β-catenin pathway. The knockdown of FGFR1 had similar effects. Additionally, miR-133b targeted and negatively regulated FGFR1. Up-regulating miR-133b or down-regulating FGFR1 could enhance the proliferation and DDP sensitivity of TNBC cells or TNBC/DDP cells. Up-regulating FGFR1 could offset the anti-TNBC cell survival and DDP sensitization shown by ectopic expression of miR-133b.

Conclusion: To sum up, miR-133b can inhibit the growth and DDP resistance of TNBC cells by targeting FGFR1 and inactivating the Wnt-β-catenin pathway.

Keywords: FGFR1; Triple negative breast cancer; Wnt-β-catenin pathway; miR-133b.