FMNL1 promotes growth and metastasis of breast cancer by inhibiting BRCA1 via upregulation of HMGA1

Abstract

Purpose: To investigate the role and mechanism of formin-like protein 1 (FMNL1) in breast cancer progression. Methods: Expression of FMNL1 in breast cancer cells was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. Colony formation and CCK8 assays were performed to assess cell proliferation. Cell migration and invasion were determined using wound-healing and Transwell assays, respectively. Results: Data from UALCAN prediction (http://ualcan.path.uab.edu/analysis.html) showed that FMNL1 was significantly upregulated in primary breast cancer tissue compared to normal tissue (p < 0.01). Enhanced FMNL1 mRNA and protein expression was also identified in breast cancer cells. shRNA-mediated FMNL1 knockdown decreased viability of breast cancer cells and reduced cell proliferation, migration, and invasion. Expression of protein high mobility group AT-hook 1 (HMGA1) was reduced, whereas breast cancer gene 1 (BRCA1) expression was enhanced, in breast cancer cells transfected with shRNA-FMNL1. Overexpression of HMGA1 attenuated FMNL1-knockdown-induced decreased HMGA1 expression and increased BRCA1 expression in breast cancer cells. BRCA1 knockdown counteracted the suppressive effects of FMNL1 silencing on breast cancer cell proliferation, migration, and invasion. Conclusion: FMNL1 promotes breast cancer cell growth and metastasis by inhibiting BRCA1 via upregulation of HMGA1, providing a potential therapeutic target for breast cancer.