Exploring the critical role of SDHA in breast cancer proliferation: implications for novel therapeutic strategies.

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作者:Khan Sikandar Ali, Iftikhar Ayesha, Haider Muhammad, Naeem Samarah, Qadeer Saima, Ashraf Asma, Abbas Afshan Syed, Hussain Mumtaz, Abdel-Maksoud Mostafa A, Alrokayan Salamn, Iqbali Ashnah, Alnumasi Tahani, Kiani Bushra Hafeez, Alamri Abdulaziz, Hameed Yasir
OBJECTIVES: This study aims to evaluate Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA) expression across various breast cancer subtypes, its prognostic significance, and the impact of SDHA knockdown on breast cancer cell functions. METHODS: To assess SDHA expression in breast cancer, we utilized multiple publicly available databases. Prognostic significance was also evaluated using relevant databases. Methylation status, and enrichment analysis were performed using the GSCA database. The mutational status of SDHA was examined using cBioPortal, and its relationship with immune infiltration and drug sensitivity was assessed. Functional assays, including cell proliferation, colony formation, wound healing, and SDHA knockdown, were performed using MCF-7 and SKBR3 breast cancer cell lines. RESULTS: Our results showed that SDHA was significantly overexpressed in breast cancer tissues compared to normal tissues. High SDHA expression was correlated with worse survival in breast cancer patients. Pathological stage analysis revealed that SDHA expression increased as the disease progressed, with lower methylation levels in tumor tissues suggesting epigenetic regulation of its expression. Functionally, SDHA knockdown in MCF-7 and SKBR3 cells led to significant reductions in cell proliferation, colony formation, and migration, highlighting its role in supporting breast cancer cell growth and metastasis. CONCLUSION: SDHA was upregulated in breast cancer and associated with poor prognosis. Our findings also suggest that SDHA plays a crucial role in promoting breast cancer cell growth and migration, indicating its therapeutic potential. Targeting SDHA could provide a novel strategy for breast cancer treatment, particularly in overcoming chemoresistance and inhibiting tumor progression.

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