MicroRNA-543 inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of triple-negative breast cancer cells via down-regulation of ACTL6A gene.

Abstract

PURPOSE:

To investigate the effect of microRNA-543 (miR-543) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells, and the associated mechanism.

METHODS:

Human breast cancer cells (MDA-MB-231, HCC1937, and MCF-7, ZR-75-1) and normal human breast epithelial cell line (MCF10A) were transfected with miR-543 mimics or inhibitor using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the mRNA and protein expression levels of miR-543, actin-like protein 6A (ACTL6A), vimentin, Snail, and E-cadherin in breast cancer cells/tissue. Cell counting kit-8 (CCK-8), wound-healing, and Transwell assays were used to measure the effect of miR-543 on TNBC cell proliferation, invasion, and migration. Overall survival was determined using data from Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis and luciferase reporter gene assay were used to determine the regulatory effect of miR-543 on ACTL6A.

RESULTS:

The level of expression of miR-543 was significantly lower in breast cancer cells/tissue than in normal human breast epithelial cell/tissue (p < 0.05). MicroRNA-543 expression level was significantly reduced in TNBC cells/tissue, relative to the other breast cancer cells/normal breast tissue (p < 0.05). MicroRNA-543 significantly suppressed tumor growth and the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, in mouse xenograft model (p < 0.05).

CONCLUSIONS:

miR-543 influences the biological behavior of TNBC cells by directly targeting ACTL6A gene. miR-543 could serve as a novel diagnostic and therapeutic target for TNBC.

• Authors: Y L Wang, R H Liang, C Y Wang, R P Zhang, S Y Wu, X Han, G L Zhang
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 24 Issue 1 Pg. 84-92 (Jan 2022) ISSN: 1699-3055 [Electronic] Italy
• PMID: 34181232 (Publication Type: Journal Article)
• Copyright: © 2021. Federación de Sociedades Españolas de Oncología (FESEO).

Chemical References

• ACTL6A protein, human
• Actins
• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• MIRN543 microRNA, human
• MicroRNAs

Topics

• Actins (physiology)
• Animals
• Cell Movement
• Cell Proliferation
• Chromosomal Proteins, Non-Histone (physiology)
• DNA-Binding Proteins (physiology)
• Down-Regulation
• Epithelial-Mesenchymal Transition
• Humans
• Mice
• MicroRNAs (physiology)
• Neoplasm Invasiveness
• Triple Negative Breast Neoplasms (pathology)
• Tumor Cells, Cultured