Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Qian Zhang¹, Hua Yang¹, Caiyi Tang², Qian Wang³, Lili Ren¹, Chao Jia⁴, Hui Zou⁵

¹Department of Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei Province 071000; ²Division of Public Health Management, The People's Hospital of Kai Zhou District, Chongqing, Hebei Province; ³Department of Clinical Laboratory and Pathology, The Hospital of the 82nd Group Army, Baoding; ⁴Department of Pharmacy, Affiliated Hospital of Hebei University, Baoding, Hebei Province 071000; ⁵Department of Hepatobiliary Pancreatic Mammary Thyroid, The People's Hospital of Kai Zhou District, Chongqing, Chongqing City 405400, China.

For correspondence:- Hui Zou Email: huizou0051@163.com Tel:+862352663968

Accepted: 30 July 2021 Published: 31 August 2021

Citation: Zhang Q, Yang H, Tang C, Wang Q, Ren L, Jia C, et al. FMNL1 promotes growth and metastasis of breast cancer by inhibiting BRCA1 via upregulation of HMGA1. Trop J Pharm Res 2021; 20(8):1559-1564 doi: 10.4314/tjpr.v20i8.2

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: Formin-like protein 1, High mobility group AT-hook 1, Breast cancer gene 1, Breast cancer, Cell growth, Metastasis