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METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.

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Endocrine, metabolic & immune disorders drug targets 2025 Vol.25(6) p. 492-502
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Li C, Xie P, Lv K, Yang Q, Mou Y

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[AIMS] This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression.

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APA Li C, Xie P, et al. (2025). METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.. Endocrine, metabolic & immune disorders drug targets, 25(6), 492-502. https://doi.org/10.2174/0118715303290063240530053252
MLA Li C, et al.. "METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.." Endocrine, metabolic & immune disorders drug targets, vol. 25, no. 6, 2025, pp. 492-502.
PMID 39021178

Abstract

[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.

MeSH Terms

Humans; Methyltransferases; RNA, Circular; Thyroid Cancer, Papillary; Tumor Suppressor Protein p53; Thyroid Neoplasms; Animals; Disease Progression; Mice; Cell Line, Tumor; Mice, Nude; Adenosine; Signal Transduction; Mice, Inbred BALB C; Gene Expression Regulation, Neoplastic; Female; Xenograft Model Antitumor Assays

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