Circ-IP6K2 suppresses tumor progression by modulating the miR-1292-5p/CAMK2N1 signal in clear cell renal cell carcinoma.

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY Functional & Integrative Genomics Pub Date : 2024-07-09 DOI:10.1007/s10142-024-01398-9
Jian-Ying Tang, Lu Yang, Qing-Jian Wu, Ying Yang, Yuan-Yuan Su, Yi-Rong Chen, Jiao Mu
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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.

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Circ-IP6K2 通过调节透明细胞肾细胞癌中的 miR-1292-5p/CAMK2N1 信号抑制肿瘤进展。
肾细胞癌(RCC)是一种起源于肾小管上皮细胞的恶性肿瘤。透明细胞 RCC 亚型因其进展迅速而与预后不良密切相关。环状 RNA(circRNA)是一类新型的调控 RNA 分子,在 ccRCC 的发展过程中发挥着作用,但其功能尚未完全阐明。在这项研究中,我们根据 GSE100186 数据集的数据,发现了 circ-IP6K2 在 ccRCC 组织中的显著下调。circ-IP6K2表达的降低与TNM分期和组织学分级的进展相关,也与ccRCC患者总生存率的降低相关。此外,我们的研究还发现,circ-IP6K2的表达抑制了体外增殖、迁移和侵袭能力,并抑制了体内异种移植的生长。从机理上讲,circ-IP6K2在ccRCC细胞中充当了miR-1292-5p的海绵,而miR-1292-5p反过来又靶向CAMK2N1的3'UTR,导致其表达下降。研究发现,CAMK2N1 是一种肿瘤抑制因子,能负向调节 β-catenin/c-Myc致癌信号通路。此外,我们还证实了circ-IP6K2和CAMK2N1在ccRCC中的表达呈正相关。Circ-IP6K2通过调节miR-1292-5p/CAMK2N1轴来阻碍ccRCC的进展。这些发现揭示了驱动ccRCC进展的分子机制,并提出了治疗ccRCC的潜在靶点。
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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
期刊最新文献
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