MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3

Authors

  • Hongxu Zhang Affiliated Hospital of Chengde Medical University
  • Minghui Wang Affiliated Hospital of Chengde Medical University
  • Zhiqiang Lang Xi'an No.3 Hospital https://orcid.org/0000-0001-9254-7270
  • Haiwang Liu Affiliated Hospital of Chengde Medical University
  • Jianping Liu Affiliated Hospital of Chengde Medical University
  • Lihui Ma Affiliated Hospital of Chengde Medical University

DOI:

https://doi.org/10.1016/j.clinsp.2022.100115

Keywords:

Breast cancer, Mir-135a-5p, Bag3, Proliferation, Migration

Abstract

Background: MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells.

Methods: Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3′UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearson's correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database.

Results: MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0/G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-β signaling pathways.

Conclusion: MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells.

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Published

2022-10-10

Issue

Section

Original Articles

How to Cite

Zhang, H., Wang, M., Lang, Z., Liu, H., Liu, J., & Ma, L. (2022). MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3. Clinics, 77, 100115. https://doi.org/10.1016/j.clinsp.2022.100115