Open AccessmiR-145-5p attenuates paclitaxel resistance and suppresses the progression in drug-resistant breast cancer cell lines
Author(s) -
Xiaojun Guan,
Yifu Guan
Publication year - 2020
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2020_190622n536
Subject(s) - paclitaxel , drug resistance , drug , cancer research , breast cancer , cancer cell lines , medicine , pharmacology , oncology , cancer , cancer cell , biology , microbiology and biotechnology
miR-145-5p has been identified as a tumor suppressor involved in a wide variety of human cancers. Herein, we aimed to further explore the functional role and molecular mechanism of miR-145-5p on breast cancer (BC) progression and chemoresistance. The expressions of miR-145-5p and sex determining region Y-box2 (SOX-2) mRNA were assessed by qRT-PCR assay. SOX2 protein expression was measured using western blot. CCK-8 assays were used to determine the IC50 values of paclitaxel (PTX) and cell proliferation. Transwell assays were performed to detect cell migration and invasion. The target of miR-145-5p was verified by dual-luciferase reporter assays. Xenograft model was used to observe the role of miR-145-5p in vivo. The results showed that miR-145-5p was downregulated in BC tissues and cells and associated with PTX resistance of BC cells. Overexpression of miR-145-5p or SOX2 knockdown repressed the proliferation, migration, invasion, and attenuated PTX resistance in PTX-resistant BC cells. Mechanistically, miR-145-5p negatively regulated SOX2 expression by targeting SOX2. The inhibitory effects of miR-145-5p on the proliferation, migration, invasion, and PTX resistance were antagonized by SOX2 level restoration in PTX-resistant BC cells. Additionally, miR-145-5p repressed tumor growth in vivo. In conclusion, our study suggested that miR-145-5p reduced PTX resistance and repressed the progression at least partly by targeting SOX2 in PTX-resistant BC cells, highlighting miR-145-5p as a promising biomarker for BC treatment.