Wu Xiaoliang, Sun Guoliang, Fan Ruixin, Liu Kai, Duan Chen, Mao Xiongmin, Wu Huahui, Yao Xiangyang, Li Bo, Chen Ke, Zhang Yangjun, Chen Zhong
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, China.
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
J Cancer. 2024 Sep 16;15(18):5876-5896. doi: 10.7150/jca.100706. eCollection 2024.
Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circSP3 to be increased in tissues from ccRCC patients and ccRCC cells, and to positively correlate with ccRCC malignant features. Knockdown of circSP3 inhibits proliferation, triggers apoptosis, and reduces migration and invasion in different ccRCC cells . Correspondingly, circSP3 overexpression Promote ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circSP3 could bind with the ribosome to initiate the translation process to encodes a novel 461-amino acid peptide referred to as SP3-461aa, which protects the MYH9 protein from proteasomal degradation. SP3-461aa played a pivotal role in mediating the oncogenic effects of circSP3 by interacting with the MYH9 protein and activating the PI3K-Akt signaling pathway. These findings suggested that circSP3 plays an important role in ccRCC development and could be a potential biomarker for the treatment and prognosis of ccRCC.
透明细胞肾细胞癌（ccRCC）是一种具有高侵袭性表型和极差预后的原发性肾癌。越来越多的证据表明，环状RNA（circRNA）在各种人类癌症的发生和发展中起关键作用。然而，circRNA在ccRCC中的表达、临床意义和调控作用在很大程度上仍不清楚。在此，我们报告circSP3在ccRCC患者组织和ccRCC细胞中表达增加，并与ccRCC的恶性特征呈正相关。敲低circSP3可抑制不同ccRCC细胞的增殖、诱导凋亡并减少迁移和侵袭。相应地，circSP3过表达在小鼠异种移植模型中促进ccRCC的致瘤性。机制上，circSP3可与核糖体结合启动翻译过程，编码一种名为SP3-461aa的新型461个氨基酸的肽，该肽可保护MYH9蛋白免受蛋白酶体降解。SP3-461aa通过与MYH9蛋白相互作用并激活PI3K-Akt信号通路，在介导circSP3的致癌作用中起关键作用。这些发现表明，circSP3在ccRCC发展中起重要作用，可能是ccRCC治疗和预后的潜在生物标志物。
