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N6-Methyladenosine-Modified circNEK11 Promotes Hepatocellular Carcinoma Progression via the miR-1236-3p/GPX2 Axis
Qian Li1,2,3,4, Xu Huang1,2,3,4, Yan Tong1,2,3,4
1School of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, P. R. China.
Abstract:
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.
Insights
Circular RNA NEK11 (circNEK11) is upregulated in hepatocellular carcinoma (HCC), promoting tumor growth and recurrence. circNEK11 may serve as a diagnostic biomarker and therapeutic target for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) play regulatory roles in cancers.
- The specific function of circNEK11 in hepatocellular carcinoma (HCC) is not well understood.
Purpose of the Study:
- Investigate the role and mechanism of circNEK11 in HCC progression.
- Determine circNEK11's potential as a biomarker for HCC.
Main Methods:
- Quantified circNEK11 expression in HCC tissues.
- Studied circNEK11's interaction with YTHDC1 and miR-1236-3p.
- Assessed circNEK11's impact on HCC cell functions in vitro and in vivo.
Main Results:
- circNEK11 expression is significantly upregulated in HCC, particularly in recurrent cases.
- circNEK11 promotes HCC cell proliferation, migration, and tumor growth.
- circNEK11 directly targets miR-1236-3p, regulating GPX2 expression and promoting HCC progression.
Conclusions:
- circNEK11 acts as an oncogenic circRNA in HCC by regulating the miR-1236-3p/GPX2 axis.
- circNEK11 is a potential diagnostic biomarker and therapeutic target for HCC.
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