Abstract

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary malignancy with high mortality. Recent findings suggest that the succinate dehydrogenase complex subunit A (SDHA) is lowly expressed in many types of cancers and involved in tumorigenesis. However, the potential regulatory roles and molecular mechanisms by which SDHA affects the development and progression of ccRCC remain largely unknown. In this study, our results showed that there was significant downregulation of SDHA in ccRCC tissue relative to corresponding non-cancerous tissue, and low expression of SDHA was associated with Fuhrman pathological grade, tumor size, TNM stage, metastasis, and poor prognosis in ccRCC patients. Moreover, overexpression of SDHA inhibited the proliferation, invasion, and migration capacities of ccRCC cells. Mechanistically, SDHA impeded the proliferation and metastasis of ccRCC cells by inactivation of the Wnt/β-catenin pathway. In vivo experiments, SDHA suppressed ccRCC growth in a nude mouse model. In conclusion, our study results indicated that SDHA may act as a new molecular marker for judging the occurrence and development of ccRCC and serve as a therapeutic target for the treatment of human ccRCC.

摘要

透明细胞肾细胞癌（ccRCC）是一种常见的泌尿生殖系统恶性肿瘤，死亡率很高。最近的研究结果表明，琥珀酸脱氢酶复合亚基 A (SDHA) 在许多类型的癌症中低表达并参与肿瘤发生。然而，SDHA 影响 ccRCC 发展和进展的潜在调节作用和分子机制仍然很大程度上未知。在本研究中，我们的结果表明，相对于相应的非癌组织，ccRCC组织中SDHA的表达显着下调，SDHA的低表达与ccRCC的Fuhrman病理分级、肿瘤大小、TNM分期、转移和预后不良有关。患者。此外，SDHA 的过表达抑制了 ccRCC 细胞的增殖、侵袭和迁移能力。机械地，在体内实验中，SDHA 在裸鼠模型中抑制了 ccRCC 的生长。总之，我们的研究结果表明，SDHA可以作为判断ccRCC发生发展的新分子标志物，作为治疗人类ccRCC的治疗靶点。