ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1594530
This article is part of the Research TopicHarnessing Molecular Insights for Enhanced Drug Sensitivity and Immunotherapy in CancerView all 30 articles
Circular RNA KIF18A promotes the progression of hepatocellular carcinoma by sponging miR-622 and upregulating CCNB1
Provisionally accepted- Peking University Third Hospital, Haidian, China
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BackgroundHepatocellular carcinoma (HCC) is a common malignant carcinoma, with increasing incidence and mortality rates. Circular RNA has been implicated in cancer progression, but the regulatory network in HCC remains unclear. This study investigates the role of a novel circRNA in HCC progression and its potential as a prognostic biomarker. MethodsThe circRNA expression profile was constructed through microarray analysis. Subcellular localization was assessed using nuclear-cytoplasmic separation and FISH. circKIF18A expression was measured by RT-qPCR, and its correlation with prognosis was analyzed using Kaplan–Meier curves. Functional assays including CCK-8, EdU, colony formation, transwell, wound-healing assays, and flow cytometry assessed HCC cell proliferation and migration. A xenograft mouse model was used to investigate the in vivo effects of circKIF18A knockdown. Bioinformatics analysis was validated by qRT-PCR and Western blot.ResultsMicroarray analysis identified circKIF18A as significantly upregulated in HCC tissues (2.57-fold, p<0.05), correlating with poor prognosis (DFS: HR=3.303, p=0.044; OS: HR=3.267, p=0.047). Functional assays demonstrated that circKIF18A knockdown inhibited HCC cell proliferation (CCK-8: 18.4-31.3% reduction, p<0.001) and migration (Transwell: 54.2-67.8% reduction, p<0.001). Mechanistic studies revealed circKIF18A acts as a miR-622 sponge to upregulate CCNB1 (p<0.01), driving cell cycle progression. In vivo, circKIF18A silencing reduced tumor growth by 95.9% (p<0.001), confirming its oncogenic role.ConclusionCircKIF18A promotes HCC progression by sponging miR-622 to upregulate CCNB1, driving cell cycle progression. Its overexpression correlates with poor prognosis, highlighting its potential as both a therapeutic target and prognostic biomarker in HCC.
Keywords: circular RNA, miRNA, Competing endogenous RNA, Hepatocellular Carcinoma, Bioinformatic analysis, cell cycle pathway
Received: 16 Mar 2025; Accepted: 22 Apr 2025.
Copyright: © 2025 Yuan, Chen, Meng, Lei, Chen, Deng, Zhao, Ren, Sadula, Li, Yuan and Bing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lei Li, Peking University Third Hospital, Haidian, China
Chunhui Yuan, Peking University Third Hospital, Haidian, China
Yuntao Bing, Peking University Third Hospital, Haidian, China
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