Unveiling the hidden role of SDHA in breast cancer proliferation: a novel therapeutic avenue

Abstract Background We observed an increased presence of succinate dehydrogenase complex subunit A (SDHA), a mitochondrial enzyme, in breast cancer (BC), which contributes to its proliferation. While SDHA deficiency has been extensively researched in rare disorders, the upregulation of SDHA and its impact on BC remain understudied. The aim of this study is to investigate the role of SDHA in BC. Methods The mRNA expression of SDHA was analyzed from TCGA, clinical BC tissues and various BC cell lines via qPCR. Immunohistochemistry was also applied to detect the SDHA expression. Our study investigated the functional outcomes of SDHA overexpression and knockdown in BC utilizing clinical BC tissues from patients and various BC cell lines (MDA-MB-453, MDA-MB-468, SKBR3, and MCF-7). Multiple web platforms and software tools, including R, HPA and TISIDB, were employed to perform comprehensive data analysis. SDHA overexpression and siSDHA were transiently transfected into the cancer cells separately to assess expression levels, cellular proliferation, and migration dynamics through colony formation assay, CCK8 assay, wound-healing analysis. Results We found that the mRNA expression level of SDHA was higher in cancer tissues or cells than in non-cancerous tissues or mammary epithelial cell in TCGA dataset, BC clinical specimens and BC cell lines, respectively. High SDHA expression was associated with poor overall survival (OS, p = 0.016) and disease specific survival (DSS, p = 0.024) in BC patients. Besides, our findings revealed MDA-MB-468, SKBR3 and MCF-7 cells transfected with siSDHA exhibited significantly reduced proliferation and migration capabilities. Conversely, the proliferation and migration abilities of these BC cells significantly increased when transfected with SDHA overexpression. Conclusions In conclusion, this study highlights the previously underestimated role of SDHA in BC proliferation, presenting a novel avenue for therapeutic intervention.