YTHDF2-regulated hsa_circ_0005882 functions as a sponge for miR-654-3p to suppress nasopharyngeal carcinoma proliferation

Xu Wang, Aiyu Ma, Lu Lu, Qiuyu Zhao, Yuzhong Yang, Xuan Meng, Yiping Sun, Shuming Wang, Zhiyi Chen, Yan Zhang, Jinhua Zheng,  Xiang Zheng

Abstract:

Circular RNAs (circRNAs) are a subclass of non-coding RNAs, playing an important regulatory role in tumor progression. Accumulating evidence has revealed that circRNAs can be regulated by m6A machinery, influencing their expression and biological functions. However, the functions and mechanisms of m6A-mediated circRNAs in nasopharyngeal carcinoma (NPC) remain to be elucidated. In this study, the sequence of hsa_circ_0005882 (circ_0005882) was determined by Sanger sequencing, and its localization in both the cytoplasm and nucleus was confirmed by fluorescence in situ hybridization. Furthermore, m6A RNA immunoprecipitation followed by qPCR (MeRIP-qPCR) and the single-base elongation- and ligation-based qPCR amplification (SELECT) assays revealed that circ_0005882 may harbor m6A modifications. Overexpression of circ_0005882 significantly suppressed NPC cell proliferation. Mechanistically, the m6A reader YTHDF2 binds to circ_0005882 to promote its degradation, thereby reducing circ_0005882 stability. Additionally, circ_0005882 functions as a sponge for miR-654-3p, contributing to the inhibition of NPC proliferation. These findings collectively demonstrate that circ_0005882, which is negatively regulated by YTHDF2, functions as a tumor suppressor by sponging miR-654-3p to inhibit NPC cell proliferation, unveiling a novel regulatory model centered on the YTHDF2/circ_0005882/miR-654-3p axis in NPC pathogenesis.