hsa_circ_0101050 regulated by ZC3H13 enhances tumorigenesis in papillary thyroid cancer via m6A modification

Abstract

While the regulatory roles of circular RNAs (circRNAs) and zinc finger CCCH-type containing 13 (ZC3H13) were previously reported in various human cancers, the mechanisms underlying their interaction in papillary thyroid cancer (PTC) remain unclear. We aimed to determine the role of hsa_circ_0101050 and its regulatory relationship with ZC3H13 in PTC. The expression levels of hsa_circ_0101050 and ZC3H13 were determined in tumor samples and adjacent normal tissues from 46 patients with PTC and in two PTC cell lines (IHH-4 and PTC-1) using quantitative reverse transcription–polymerase chain reaction. The roles of hsa_circ_0101050 and ZC3H13 in cell viability, wound healing, and migration were determined using knockdown and overexpression approaches in PTC cell lines, and a xenograft model in nude mice was used to determine their role in vivo. Methylated RNA immunoprecipitation assay was used to analyze N6-methyladenosine (m6A) modification of hsa_circ_0101050 by ZC3H13. We found hsa_circ_0101050 overexpression and ZC3H13 downregulation in PTC samples and PTC cell lines. In PTC cell lines, silencing hsa_circ_0101050 reduced cell viability and migration whereas its overexpression promoted an aggressive PTC phenotype. ZC3H13 increased the m6A modification of hsa_circ_0101050 and repressed its expression. ZC3H13 overexpression inhibited PTC cell viability, migration, and invasion, which were reversed in cells overexpressing hsa_circ_0101050. Taken together, these results suggested that the downregulation of hsa_circ_0101050 mediated by ZC3H13 through m6A modification contributed to its oncogenic effect in PTC development, revealing the ZC3H13–m6A–hsa_circ_0101050 as a potential therapeutic target in PTC.

Keywords

• hsa_circ_0101050
• ZC3H13
• m6A modification
• Papillary thyroid cancer