HOXC13 promotes cell proliferation, metastasis and glycolysis in breast cancer by regulating DNMT3A

Hongrui Li; Pengcheng Gao; Haifeng Chen; Junjie Zhao; Xiangzhong Zhang; Ganggang Li; Liting Wang; Long Qin

doi:10.3892/etm.2023.12138

HOXC13 promotes cell proliferation, metastasis and glycolysis in breast cancer by regulating DNMT3A

Exp Ther Med. 2023 Jul 31;26(3):439. doi: 10.3892/etm.2023.12138. eCollection 2023 Sep.

Authors

Hongrui Li^{1

2}, Pengcheng Gao^{1

2}, Haifeng Chen^{1

2}, Junjie Zhao^{1

2}, Xiangzhong Zhang^{1

2}, Ganggang Li^{1

2}, Liting Wang^{1

2}, Long Qin^{1

2}

Affiliations

¹ Department of Thyroid and Breast Diseases, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China.
² Department of Thyroid and Breast Diseases, Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China.

Abstract

Breast cancer (BC) is a life-threatening malignant tumor that affects females more commonly than males. The mechanisms underlying BC proliferation, metastasis and glycolysis require further investigation. Homeobox C13 (HOXC13) is highly expressed in BC; however, the specific mechanisms in BC are yet to be fully elucidated. Therefore, the aim of the present study was to investigate the role of HOXC13 in BC proliferation, migration, invasion and glycolysis. In the present study, the UALCAN database was used to predict the expression levels of HOXC13 in patients with BC. Western blot analysis and reverse transcription-quantitative PCR were used to determine the expression levels of HOXC13 in BC cell lines. Moreover, HOXC13 knockdown was induced using cell transfection, and the viability, proliferation and apoptosis of cells were detected using Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining and flow cytometry. Migration, invasion and epithelial-mesenchymal transition (EMT) were measured using wound healing assay, Transwell assay and western blotting. In addition, XF96 extracellular flux analyzer and corresponding kits were used to detect glycolysis. The JASPAR database was used to predict promoter binding sites for the transcription factors HOXC13 and DNA methyltransferase 3α (DNMT3A). HOXC13 expression was silenced and DNMT3A was simultaneously overexpressed using cell transfection. The results of the present study revealed that HOXC13 expression was significantly elevated in BC tissues and cells. Following HOXC13 knockdown in BC cells, the viability, proliferation, glycolysis, migration, invasion and EMT were significantly decreased, and apoptosis was significantly increased. In addition, HOXC13 positively regulated the transcription of DNMT3A in BC cells, thus playing a regulatory role in the malignant progression of cells. In conclusion, HOXC13 promoted cell viability, proliferation, migration, invasion, EMT and glycolysis in BC by regulating DNMT3A.

Keywords: DNA methyltransferase 3α; breast cancer; glycolysis; homeobox C13; metastasis; proliferation.

Grants and funding

Funding: No funding was received.