Luo Lan, Sun Yanlei, Cao Zongli
Department of Health Management (physical examination), The third People's Hospital of Hubei Province, Wuhan, China.
Department of Endocrinology, Wuhan Third Hospital, Wuhan, China.
DNA Cell Biol. 2025 Feb;44(2):99-108. doi: 10.1089/dna.2024.0197. Epub 2024 Dec 2.
The number of cases of papillary thyroid cancer (PTC) has gone up significantly in recent years, with high recurrence. Numerous reports have highlighted the participation of circular RNAs (circRNAs) in regulating the advancement of cancers, including PTC. Furthermore, recent studies suggest that N6-methyladenosine (m6A) modified circRNAs play pivotal roles in cancer progression. Hence, we studied the potential role of a novel circRNA, hsa_circ_0136959, and its regulatory mechanism on m6A modification by methyltransferase-like 3 (METTL3) in the tumor characteristics of PTC. The expressions of hsa_circ_0136959 and were evaluated in PTC samples and cell lines via quantitative real-time polymerase chain reaction. The effect of hsa_circ_0136959 on the malignant properties of PTC was analyzed by performing Cell Counting Kit-8, colony formation, and transwell assays. In addition, its effects on the levels of markers related to ferroptosis (reactive oxygen species, Fe, and iron) in PTC cells were also assessed. Bioinformatics analysis was done to determine the hsa_circ_0136959 expression and m6A modification sites on it in PTC. The m6A level of hsa_circ_0136959 was analyzed through methylated (m6A) RNA immunoprecipitation. The hsa_circ_0136959 was observed to be downregulated in both PTC samples and cells. experiments showed that its overexpression impeded the malignant properties of PTC cells. Moreover, hsa_circ_0136959 overexpression increased the levels of ferroptosis-related markers in PTC cells. We also found that was notably reduced in PTC samples and was positively correlated with hsa_circ_0136959. Mechanistically, METTL3 enhanced hsa_circ_0136959 expression through m6A modification. Our results demonstrate that METTL3-mediated m6A modification elevated hsa_circ_0136959 expression and subsequently restricted the tumor characteristics of PTC by accelerating ferroptosis.
近年来，甲状腺乳头状癌（PTC）的病例数显著上升，且复发率高。众多报道强调了环状RNA（circRNA）在包括PTC在内的癌症进展调控中的作用。此外，最近的研究表明，N6-甲基腺苷（m6A）修饰的circRNA在癌症进展中起关键作用。因此，我们研究了一种新型circRNA，即hsa_circ_0136959的潜在作用及其通过甲基转移酶样3（METTL3）对m6A修饰的调控机制在PTC肿瘤特征中的作用。通过定量实时聚合酶链反应评估hsa_circ_0136959在PTC样本和细胞系中的表达。通过进行细胞计数试剂盒-8、集落形成和Transwell实验分析hsa_circ_0136959对PTC恶性特性的影响。此外，还评估了其对PTC细胞中与铁死亡相关标志物（活性氧、铁和铁离子）水平的影响。进行生物信息学分析以确定PTC中hsa_circ_0136959的表达及其上的m6A修饰位点。通过甲基化（m6A）RNA免疫沉淀分析hsa_circ_0136959的m6A水平。观察到hsa_circ_0136959在PTC样本和细胞中均下调。实验表明，其过表达可抑制PTC细胞的恶性特性。此外，hsa_circ_0136959过表达增加了PTC细胞中铁死亡相关标志物的水平。我们还发现，在PTC样本中显著降低，且与hsa_circ_0136959呈正相关。机制上，METTL3通过m6A修饰增强了hsa_circ_0136959的表达。我们的结果表明，METTL3介导的m6A修饰提高了hsa_circ_0136959的表达，随后通过加速铁死亡限制了PTC的肿瘤特征。
