Altered Expression of Mitochondrial Succinate Dehydrogenase Subunit D Influences Breast Cancer Progression

Mitochondrial succinate dehydrogenase subunits are differentially expressed in multiple tumor types, suggesting their role as a cancer type-dependent metabolic target. However, information on the expression of SDH subunits in breast cancer (BC), particularly in South Asian populations, remains scarce. So, we analyze the expression profile of all four SDH subunits in breast cancer patients from Bangladesh. qRT-PCR was carried out to analyze the mRNA expression of four SDH subunits in Luminal A, Luminal B, Her2+, and triple-negative breast cancer subtypes and the results were compared with The Cancer Genome Atlas (TCGA) database. All four succinate dehydrogenase subunits were significantly upregulated in tumor tissues when compared to controls and showed an alignment with the TCGA except SDHD, which was significantly downregulated in TCGA. Subtype-specific analysis demonstrated differential expression patterns. SDHD upregulation has also been connected to worse outcomes for patients which indicates its role in cancer progression. Furthermore, we found a significant upregulation of METTL3 in our patient cohort. Taken together, the elevated SDHD and METTL3 expression suggests a potential epigenetic mechanism-driven SDHD activation, highlighting its previously unreported role in breast cancer biology and revealing a distinct pattern of SDH dysregulation in the Bangladeshi breast cancer population.