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TMEM45A的上调在体外促进了透明细胞肾细胞癌的进展。

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro.

作者信息

Jiang Huiming, Chen Haibin, Wan Pei, Liang Meng, Chen Nanhui

机构信息

Department of Urology, Meizhou People's Hospital, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, People's Republic of China.

Department of Histology and Embryology, Shantou University Medical College, Shantou, People's Republic of China.

出版信息

J Inflamm Res. 2021 Dec 1;14:6421-6430. doi: 10.2147/JIR.S341596. eCollection 2021.

Abstract

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of primary kidney cancer worldwide. Transmembrane protein 45A (TMEM45A) has been reported to be closely associated with the progression of several cancers. However, the role of TMEM45A in ccRCC remains unclear. Our study intended to explore the potential role of TMEM45A in ccRCC.

METHODS

Data on the expression of TMEM45A were obtained from multiple databases, including UCSC, GEPIA2, Oncomine and TIMER. Real-world samples of ccRCC and paired normal renal tissues were used to confirm the information obtained from the databases. In addition, the prognostic value of TMEM45A was evaluated. Loss-of-function assays were performed using TMEM45A-targeting lentivirus to evaluate the biological role of TMEM45A in renal cancer cells. Gene set enrichment analysis (GSEA) was performed to investigate the potential molecular mechanisms.

RESULTS

TMEM45A was significantly overexpressed in patients with ccRCC and correlated with poor overall survival and disease-free survival. In addition, the expression of TMEM45A was closely associated with various clinicopathological parameters such as histological grade and TNM stage. Knockdown of TMEM45A inhibited the proliferation and migration and promoted the apoptosis of ccRCC cells in vitro. The results of the GSEA suggested that TMEM45A was potentially involved in the promotion of epithelial-mesenchymal transition (EMT) and inflammatory response in ccRCC.

CONCLUSION

TMEM45A was overexpressed and associated with poor survival and acted as a tumour promoter in ccRCC; therefore, might be a potential prognostic marker and therapeutic target.

摘要

背景

透明细胞肾细胞癌(ccRCC)是全球最常见且侵袭性最强的原发性肾癌类型。据报道,跨膜蛋白45A(TMEM45A)与多种癌症的进展密切相关。然而,TMEM45A在ccRCC中的作用仍不清楚。我们的研究旨在探讨TMEM45A在ccRCC中的潜在作用。

方法

从包括UCSC、GEPIA2、Oncomine和TIMER在内的多个数据库中获取TMEM45A的表达数据。使用ccRCC的实际样本和配对的正常肾组织来证实从数据库中获得的信息。此外,评估了TMEM45A的预后价值。使用靶向TMEM45A的慢病毒进行功能丧失实验,以评估TMEM45A在肾癌细胞中的生物学作用。进行基因集富集分析(GSEA)以研究潜在的分子机制。

结果

TMEM45A在ccRCC患者中显著过表达,且与总体生存率和无病生存率差相关。此外,TMEM45A的表达与各种临床病理参数密切相关,如组织学分级和TNM分期。在体外,敲低TMEM45A可抑制ccRCC细胞的增殖和迁移,并促进其凋亡。GSEA结果表明,TMEM45A可能参与促进ccRCC中的上皮-间质转化(EMT)和炎症反应。

结论

TMEM45A在ccRCC中过表达,与不良生存相关,并作为肿瘤促进因子发挥作用;因此,它可能是一种潜在的预后标志物和治疗靶点。

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