METTL3介导的hsa_circ_0131922的m6A修饰通过调控p53通路减弱甲状腺乳头状癌的进展。
METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.
作者信息
Li Chan, Xie Ping, Lv Kun, Yang Qian, Mou Yanjie
机构信息
Department of Tradition Chinese Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan 450060, Hubei, China.
出版信息
Endocr Metab Immune Disord Drug Targets. 2025;25(6):492-502. doi: 10.2174/0118715303290063240530053252.
AIMS
This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression.
BACKGROUND
Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented.
OBJECTIVE
In this work, we aimed to examine the molecular mechanisms of a novel m6Amodified circRNA, hsa_circ_0131922, in PTC progression.
METHODS
Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments.
RESULTS
The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 and .
CONCLUSION
The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.
目的
本研究旨在证实环状RNA（circRNA）hsa_circ_0131922在甲状腺乳头状癌（PTC）进展中的调控作用及机制。
背景
越来越多的证据表明，N6-甲基腺苷（m6A）修饰的环状RNA（circRNA）在各种恶性肿瘤中发挥关键作用。然而，由METTL3介导的circRNA的m6A修饰在甲状腺乳头状癌（PTC）中的具体作用仍未得到证实。
目的
在本研究中，我们旨在探讨一种新型m6A修饰的circRNA，hsa_circ_0131922，在PTC进展中的分子机制。
方法
从GEO数据集中鉴定潜在的circRNA。通过qRT-PCR或蛋白质免疫印迹法检测hsa_circ_0131922、METTL3、p53和p21的RNA或蛋白质水平。通过CCK8、伤口愈合、transwell和异种移植肿瘤实验检测各种细胞功能。进行MeRIP-qPCR以观察METTL3介导的hsa_circ_0131922的m6A修饰。此外，通过生物信息学分析和各种挽救实验分析PTC中hsa_circ_0131922与METTL3之间的相互作用。
结果
hsa_circ_0131922水平在PTC组织和细胞系中显著下调。此外，较低的hsa_circ_0131922水平与PTC患者的不良预后相关。hsa_circ_0131922过表达降低了PTC细胞的恶性表型并激活了p53/p21通路。生物信息学分析显示了hsa_circ_0131922的m6A修饰位点，以及hsa_circ_0131922与METTL3之间的正相关。此外，METTL3过表达增加了hsa_circ_0131922的m6A修饰水平。机制上，已发现hsa_circ_0131922过表达的抗肿瘤作用可通过沉默METTL3部分逆转。
结论
结果表明METTL3对hsa_circ_0131922进行m6A修饰，通过调节p53通路减弱PTC的进展。因此，hsa_circ_0131922可能是PTC的预测性预后生物标志物和治疗靶点。
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