N6-Methyladenosine-Modified circNEK11 Promotes Hepatocellular Carcinoma Progression via the miR-1236-3p/GPX2 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.