Xu Ning, Xiao Wen, Meng Xiangui, Li Weiquan, Wang Xuegang, Zhang Xiaoping, Yang Hongmei
Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cell Death Discov. 2022 Aug 4;8(1):351. doi: 10.1038/s41420-022-01145-8.
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for its metastasis remain scarce. We analyzed clinical samples and public database, for differential expression of SLC27A2 and further explored its relationship with clinical prognosis. Biochemistry and functional experiments were carried out to study the potential mechanisms of SLC27A2, CDK3, and EMT. SLC27A2 was significantly downregulated in clinical specimens and renal cancer cell lines and predicted poor prognosis. We found that specific upregulation of SLC27A2 could significantly inhibited the proliferation, migration, and invasion of renal cancer cell lines. SLC27A2 could also influence the Epithelial-mesenchymal transition (EMT) signaling pathway, linked to the progression and metastasis of renal cancer. Using whole transcriptome sequencing of SLC27A2, CDK3 was identified as a regulatory SLC27A2 target. In terms of mechanism, SLC27A2 may further inhibit the epithelial-to-mesenchymal transition by negatively regulating CDK3. Our work suggests that functional inhibition of SLC27A2-CDK3-EMT axis may be an attractive therapeutic target for metastasis of ccRCC.
透明细胞肾细胞癌（ccRCC）是泌尿系统最常见的恶性肿瘤之一。远处转移是ccRCC预后不良的主要原因。然而，发现ccRCC对放疗和化疗反应不佳。针对其转移的有效治疗策略仍然匮乏。我们分析了临床样本和公共数据库，以研究SLC27A2的差异表达，并进一步探讨其与临床预后的关系。进行了生物化学和功能实验，以研究SLC27A2、CDK3和上皮-间质转化（EMT）的潜在机制。SLC27A2在临床标本和肾癌细胞系中显著下调，并预示预后不良。我们发现特异性上调SLC27A2可显著抑制肾癌细胞系的增殖、迁移和侵袭。SLC27A2还可影响与肾癌进展和转移相关的上皮-间质转化（EMT）信号通路。通过对SLC27A2进行全转录组测序，确定CDK3为SLC27A2的调控靶点。在机制方面，SLC27A2可能通过负向调节CDK3进一步抑制上皮-间质转化。我们的研究表明，抑制SLC27A2-CDK3-EMT轴的功能可能是ccRCC转移的一个有吸引力的治疗靶点。
