Abstract：
Renal cell carcinoma (RCC) is a malignant tumor originating from the epithelial cells of the renal tubules. The clear cell RCC subtype is closely linked to a poor prognosis due to its rapid progression. Circular RNA (circRNA) is a novel class of regulatory RNA molecules that play a role in the development of ccRCC, although their functions have not been fully elucidated. In this study, we identified a significant downregulation of circ-IP6K2 in ccRCC tissues based on data from the GSE100186 dataset. The decreased expression of circ-IP6K2 correlated with the progression of TNM stage and histological grade, and was also associated with decreased overall survival rates in ccRCC patients. Moreover, our findings revealed that circ-IP6K2 expression suppressed proliferation, migration, and invasion capabilities in vitro, and inhibited xenograft growth in vivo. Mechanistically, circ-IP6K2 acted as a sponge for miR-1292-5p in ccRCC cells, which in turn targeted the 3\'UTR of CAMK2N1, leading to a decrease in its expression. CAMK2N1 was identified as a tumor suppressor that negatively regulated the β-catenin/c-Myc oncogenic signaling pathway. Additionally, we confirmed a positive correlation between the expression of circ-IP6K2 and CAMK2N1 in ccRCC. Circ-IP6K2 functions to impede the progression of ccRCC by modulating the miR-1292-5p/CAMK2N1 axis. These findings shed new light on the molecular mechanisms driving ccRCC progression and suggest potential therapeutic targets for the treatment of ccRCC.
摘要：
肾细胞癌（RCC）是起源于肾小管上皮细胞的恶性肿瘤。透明细胞RCC亚型由于其快速进展而与不良预后密切相关。环状RNA（circularRNA，circRNA）是一类新型的调控RNA分子，在ccRCC的发展中起作用。尽管它们的功能尚未完全阐明。在这项研究中,根据GSE100186数据集的数据,我们发现ccRCC组织中circ-IP6K2的显著下调.circ-IP6K2的表达降低与TNM分期和组织学分级有关。并且还与ccRCC患者的总体生存率降低有关。此外，我们的发现表明，circ-IP6K2表达抑制增殖，迁移,和体外侵袭能力，并抑制体内异种移植物的生长。机械上,ccRCC细胞中circ-IP6K2充当miR-1292-5p的海绵，进而靶向CAMK2N1的3'UTR，导致其表达减少。CAMK2N1被鉴定为负调控β-连环蛋白/c-Myc致癌信号通路的肿瘤抑制因子。此外,我们证实ccRCC中circ-IP6K2和CAMK2N1的表达呈正相关。Circ-IP6K2通过调节miR-1292-5p/CAMK2N1轴来阻止ccRCC的进展。这些发现为驱动ccRCC进展的分子机制提供了新的思路，并提出了治疗ccRCC的潜在治疗靶点。
