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ISSN 1338-4317 (online)

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neo_2020_190622N536

Title: miR-145-5p attenuates paclitaxel resistance and suppresses the progression in drug-resistant breast cancer cell lines
Author: X. GUAN, Y. GUAN

Abstract: 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.

Keywords: MiR-145-5p; sex determining region Y-box2 (SOX-2); paclitaxel (PTX) resistance; drug-resistant BC cells
Published online: 14-May-2020
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2020_190622N536


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