<scp>N6</scp> ‐Methyladenosine‐Modified <scp>circNEK11</scp> Promotes Hepatocellular Carcinoma Progression via the <scp>miR</scp> ‐1236‐3p/ <scp>GPX2</scp> Axis
circRNAs are endogenous covalently closed circular RNAs, and previous studies have validated their key regulatory roles in malignant tumors; however, the specific role and regulatory mechanism of circNEK11 in hepatocellular carcinoma (HCC) remain unclear. Here, we discovered that circNEK11 back-spliced from exons 12, 13, 14, and 15 of the NEK11 gene is significantly upregulated in HCC tissues, especially recurrent HCC tissues. YTHDC1 functions as a reader of m6A-modified circNEK11 and facilitates its cytoplasmic export. circNEK11 promotes HCC cell oncogenic functions in vitro and HCC growth in vivo. Mechanistically, circNEK11 directly binds to miR-1236-3p to regulate GPX2 expression, thus promoting HCC progression and recurrence. Collectively, our findings suggest that circNEK11 is a potential biomarker and target for HCC diagnosis and treatment.
Authors
- Heng Dong (ORCID: https://orcid.org/0000-0002-2537-7950)
- Fangtian Bu
- Shuanghong Yan (ORCID: https://orcid.org/0000-0002-3292-2830)
- Jie Ying
- Yan Tong (ORCID: https://orcid.org/0000-0002-7610-8259)
- Cunjie Chang
- Jianxiang Chen (ORCID: https://orcid.org/0000-0002-8193-191X)
- Qian Li (ORCID: https://orcid.org/0000-0002-2560-5730)
- Xu Huang (ORCID: https://orcid.org/0000-0002-1619-276X)
- Minghui Song (ORCID: https://orcid.org/0009-0003-5311-1011)
- C.-C. Yong
Institutions
- Hangzhou Normal University (CN)
- Affiliated Hospital of Hangzhou Normal University (CN)
- Nanjing Jiangning Hospital (CN)
Publication Details
- Journal
- Cancer Science
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1111/cas.70203
- Citations
- 2
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Zhejiang Province