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

IF 6 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2025-03-21 DOI:10.1186/s12935-025-03746-6

Liyun Yong, Yuan Fang, Lingli Jin, Xiuqin Zhang, Manuel A Luis, Xiaoyan Lin, Shasha Tang, Fengfeng Cai

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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.

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揭示SDHA在乳腺癌增殖中的隐藏作用：一种新的治疗途径。

背景：我们观察到琥珀酸脱氢酶复合物亚基A (SDHA)，一种线粒体酶，在乳腺癌（BC）中增加，这有助于其增殖。虽然SDHA缺乏症在罕见疾病中得到了广泛的研究，但SDHA的上调及其对BC的影响仍未得到充分研究。本研究的目的是探讨SDHA在BC中的作用。方法：采用qPCR方法对TCGA、临床BC组织和各种BC细胞系的SDHA mRNA表达进行分析。免疫组化法检测SDHA的表达。我们的研究利用来自患者的临床BC组织和各种BC细胞系（MDA-MB-453、MDA-MB-468、SKBR3和MCF-7）研究了SDHA在BC中过表达和敲低的功能结果。采用R、HPA、TISIDB等多种web平台和软件工具进行综合数据分析。将SDHA过表达和siSDHA分别瞬时转染到癌细胞中，通过集落形成实验、CCK8实验和伤口愈合分析来评估表达水平、细胞增殖和迁移动态。结果：我们发现，在TCGA数据集、BC临床标本和BC细胞系中，SDHA在癌组织或细胞中的mRNA表达水平分别高于非癌组织或乳腺上皮细胞。在BC患者中，高SDHA表达与较差的总生存期（OS, p = 0.016）和疾病特异性生存期（DSS, p = 0.024）相关。此外，我们的研究结果显示，转染了siSDHA的MDA-MB-468、SKBR3和MCF-7细胞的增殖和迁移能力显著降低。相反，当转染过表达SDHA时，这些BC细胞的增殖和迁移能力显著增强。结论：总之，本研究强调了SDHA在BC增殖中的作用，为治疗干预提供了新的途径。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.