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探索SDHA在乳腺癌增殖中的关键作用:对新型治疗策略的启示

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

作者信息

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

机构信息

Department of Biochemistry, Peshawar Medical and Dental College, Affiliated with Riphah International University Islamabad Peshawar, Pakistan.

Department of Pharmacology, Rehman Medical College Peshawar, Pakistan.

出版信息

Am J Transl Res. 2025 Jul 15;17(7):5221-5240. doi: 10.62347/XAKQ8090. eCollection 2025.

Abstract

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.

摘要

目的

本研究旨在评估琥珀酸脱氢酶复合物黄素蛋白亚基A(SDHA)在各种乳腺癌亚型中的表达、其预后意义以及SDHA敲低对乳腺癌细胞功能的影响。

方法

为评估SDHA在乳腺癌中的表达,我们利用了多个公开可用的数据库。还使用相关数据库评估了预后意义。使用GSCA数据库进行甲基化状态和富集分析。使用cBioPortal检查SDHA的突变状态,并评估其与免疫浸润和药物敏感性的关系。使用MCF-7和SKBR3乳腺癌细胞系进行了包括细胞增殖、集落形成、伤口愈合和SDHA敲低在内的功能测定。

结果

我们的结果表明,与正常组织相比,SDHA在乳腺癌组织中显著过表达。SDHA高表达与乳腺癌患者较差的生存率相关。病理分期分析显示,随着疾病进展,SDHA表达增加,肿瘤组织中较低的甲基化水平表明其表达的表观遗传调控。在功能上,MCF-7和SKBR3细胞中SDHA的敲低导致细胞增殖、集落形成和迁移显著减少,突出了其在支持乳腺癌细胞生长和转移中的作用。

结论

SDHA在乳腺癌中上调并与不良预后相关。我们的研究结果还表明,SDHA在促进乳腺癌细胞生长和迁移中起关键作用,表明其治疗潜力。靶向SDHA可为乳腺癌治疗提供一种新策略,特别是在克服化疗耐药性和抑制肿瘤进展方面。

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