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Volume 25, Issue 6
  • ISSN: 1871-5303
  • E-ISSN: 2212-3873

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 m6A-modified 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.

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2024-07-15
2025-05-28

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References

  1. MulitaF. AnjumF. Thyroid Adenoma, In: StatPearls; Ineligible companies. Disclosure: Fatima Anjum declares no relevant financial relationships with ineligible companies: Treasure Island (FL) , 2024
     [Google Scholar]
  2. KrajewskaJ. KukulskaA. Oczko-WojciechowskaM. Kotecka-BlicharzA. Drosik-RutowiczK. Haras-GilM. JarzabB. Handkiewicz-JunakD. Early diagnosis of low-risk papillary thyroid cancer results rather in overtreatment than a better survival.Front. Endocrinol.20201157142110.3389/fendo.2020.571421 33123090
     [Google Scholar]
  3. UlisseS. BaldiniE. LauroA. PironiD. TripodiD. LoriE. FerentI.C. AmabileM.I. CataniaA. Di MatteoF.M. ForteF. SantoroA. PalumboP. D’AndreaV. SorrentiS. Papillary thyroid cancer prognosis: An evolving field.Cancers 20211321556710.3390/cancers13215567 34771729
     [Google Scholar]
  4. Coca-PelazA. ShahJ.P. Hernandez-PreraJ.C. GhosseinR.A. RodrigoJ.P. HartlD.M. OlsenK.D. ShahaA.R. ZafereoM. SuarezC. NixonI.J. RandolphG.W. MäkitieA.A. KowalskiL.P. Vander PoortenV. SanabriaA. Guntinas-LichiusO. SimoR. ZbärenP. AngelosP. KhafifA. RinaldoA. FerlitoA. Papillary thyroid cancer—aggressive variants and impact on management: A narrative review.Adv. Ther.20203773112312810.1007/s12325‑020‑01391‑1 32488657
     [Google Scholar]
  5. BibleK.C. KebebewE. BrierleyJ. BritoJ.P. CabanillasM.E. ClarkT.J.Jr Di CristofanoA. FooteR. GiordanoT. KasperbauerJ. NewboldK. NikiforovY.E. RandolphG. RosenthalM.S. SawkaA.M. ShahM. ShahaA. SmallridgeR. Wong-ClarkC.K. 2021 american thyroid association guidelines for management of patients with anaplastic thyroid cancer.Thyroid202131333738610.1089/thy.2020.0944 33728999
     [Google Scholar]
  6. AbdullahM.I. JunitS.M. NgK.L. JayapalanJ.J. KarikalanB. HashimO.H. Papillary thyroid cancer: Genetic alterations and molecular biomarker investigations.Int. J. Med. Sci.201916345046010.7150/ijms.29935 30911279
     [Google Scholar]
  7. GuoD. LiF. ZhaoX. LongB. ZhangS. WangA. CaoD. SunJ. LiB. Circular RNA expression and association with the clinicopathological characteristics in papillary thyroid carcinoma.Oncol. Rep.202044251953210.3892/or.2020.7626 32468074
     [Google Scholar]
  8. YarmishynA.A. IsholaA.A. ChenC.Y. VerusingamN.D. RengganatenV. MustaphaH.A. ChuangH.K. TengY.C. PhungV.L. HsuP.K. LinW.C. MaH.I. ChiouS.H. WangM.L. Circular RNAs modulate cancer hallmark and molecular pathways to support cancer progression and metastasis.Cancers 202214486210.3390/cancers14040862 35205610
     [Google Scholar]
  9. YeM. HouH. ShenM. DongS. ZhangT. Circular RNA circFOXM1 plays a role in papillary thyroid carcinoma by sponging miR-1179 and regulating HMGB1 expression.Mol. Ther. Nucleic Acids20201974175010.1016/j.omtn.2019.12.014 31951855
     [Google Scholar]
  10. ChuJ. TaoL. YaoT. ChenZ. LuX. GaoL. FangL. ChenJ. HeG. ShenS. ZhangD. Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression.Cell Death Dis.202112111210.1038/s41419‑020‑03350‑8 33479208
     [Google Scholar]
  11. LiC. ZhuL. FuL. HanM. LiY. MengZ. QiuX. CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways.Diagn. Pathol.20211619310.1186/s13000‑021‑01153‑9 34689819
     [Google Scholar]
  12. Di TimoteoG. DattiloD. Centrón-BrocoA. ColantoniA. GuarnacciM. RossiF. IncarnatoD. OlivieroS. FaticaA. MorlandoM. BozzoniI. Modulation of circRNA metabolism by m6A modification.Cell Rep.202031610764110.1016/j.celrep.2020.107641 32402287
     [Google Scholar]
  13. WuJ. GuoX. WenY. HuangS. YuanX. TangL. SunH. N6-methyladenosine modification opens a new chapter in circular RNA biology.Front. Cell Dev. Biol.2021970929910.3389/fcell.2021.709299 34368159
     [Google Scholar]
  14. ChenX. LuT. CaiY. HanY. DingM. ChuY. ZhouX. WangX. KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway.Cell. Mol. Biol. Lett.20232813210.1186/s11658‑023‑00445‑w 37076815
     [Google Scholar]
  15. ZaccaraS. RiesR.J. JaffreyS.R. Reading, writing and erasing mRNA methylation.Nat. Rev. Mol. Cell Biol.2019201060862410.1038/s41580‑019‑0168‑5 31520073
     [Google Scholar]
  16. JiangX. LiuB. NieZ. DuanL. XiongQ. JinZ. YangC. ChenY. The role of m6A modification in the biological functions and diseases.Signal Transduct. Target. Ther.2021617410.1038/s41392‑020‑00450‑x 33611339
     [Google Scholar]
  17. HeR.Z. JiangJ. LuoD.X. M6A modification of circNSUN2 promotes colorectal liver metastasis.Genes Dis.2021816710.1016/j.gendis.2019.12.002 33569509
     [Google Scholar]
  18. RaoX. LaiL. LiX. WangL. LiA. YangQ.N. 6 ‐methyladenosine modification of circular RNA CIRC‐ARL3 facilitates HEPATITIS B VIRUS ‐associated hepatocellular carcinoma via sponging MIR ‐1305.IUBMB Life202173240841710.1002/iub.2438 33372396
     [Google Scholar]
  19. ZhangC. WangJ. GengX. TuJ. GaoH. LiL. ZhouX. WuH. JingJ. PanW. MouY. Circular RNA expression profile and m6A modification analysis in poorly differentiated adenocarcinoma of the stomach.Epigenomics202012121027104010.2217/epi‑2019‑0153 32657141
     [Google Scholar]
  20. TianQ. MuQ. LiuS. HuangK. TangY. ZhangP. ZhaoJ. ShuC. m6A- modified circASXL1 promotes proliferation and migration of ovarian cancer through the miR-320d/RACGAP1 axis.Carcinogenesis2023441285987010.1093/carcin/bgad066 37738681
     [Google Scholar]
  21. WuQ. YinX. ZhaoW. XuW. ChenL. Molecular mechanism of m6A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells.Cell Death Discov.20228122910.1038/s41420‑022‑00979‑6 35474040
     [Google Scholar]
  22. WuA. HuY. XuY. XuJ. WangX. CaiA. LiuR. ChenL. WangF. Methyltransferase-like 3-mediated m6a methylation of Hsa_circ_0058493 accelerates hepatocellular carcinoma progression by binding to YTH domain-containing protein 1.Front. Cell Dev. Biol.2021976258810.3389/fcell.2021.762588 34888309
     [Google Scholar]
  23. ChenC. YuanW. ZhouQ. ShaoB. GuoY. WangW. YangS. GuoY. ZhaoL. DangQ. YangX. WangG. KangQ. JiZ. LiuJ. SunZ. N6-methyladenosine-induced circ1662 promotes metastasis of colorectal cancer by accelerating YAP1 nuclear localization.Theranostics20211194298431510.7150/thno.51342 33754062
     [Google Scholar]
  24. ChenR.X. ChenX. XiaL.P. ZhangJ.X. PanZ.Z. MaX.D. HanK. ChenJ.W. JuddeJ.G. DeasO. WangF. MaN.F. GuanX. YunJ.P. WangF.W. XuR.H. Dan,Xie N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis.Nat. Commun.2019101469510.1038/s41467‑019‑12651‑2 31619685
     [Google Scholar]
  25. Hernández BorreroL.J. El-DeiryW.S. Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochim. Biophys. Acta Rev. Cancer20211876118855610.1016/j.bbcan.2021.188556 33932560
     [Google Scholar]
  26. SongE. JeonM.J. OhH.S. HanM. LeeY.M. KimT.Y. ChungK.W. KimW.B. ShongY.K. SongD.E. KimW.G. Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classic papillary thyroid carcinoma?Eur. J. Endocrinol.2018179313514210.1530/EJE‑17‑0991 29875289
     [Google Scholar]
  27. VoJ.N. CieslikM. ZhangY. ShuklaS. XiaoL. ZhangY. WuY.M. DhanasekaranS.M. EngelkeC.G. CaoX. RobinsonD.R. NesvizhskiiA.I. ChinnaiyanA.M. The landscape of circular RNA in cancer.Cell20191764869881.e1310.1016/j.cell.2018.12.021 30735636
     [Google Scholar]
  28. KristensenL.S. JakobsenT. HagerH. KjemsJ. The emerging roles of circRNAs in cancer and oncology.Nat. Rev. Clin. Oncol.202219318820610.1038/s41571‑021‑00585‑y 34912049
     [Google Scholar]
  29. YaoY. ChenX. YangH. ChenW. QianY. YanZ. LiaoT. YaoW. WuW. YuT. ChenY. ZhangY. Hsa_circ_0058124 promotes papillary thyroid cancer tumorigenesis and invasiveness through the NOTCH3/GATAD2A axis.J. Exp. Clin. Cancer Res.201938131810.1186/s13046‑019‑1321‑x 31324198
     [Google Scholar]
  30. CaiX. ZhaoZ. DongJ. LvQ. YunB. LiuJ. ShenY. KangJ. LiJ. Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression.Cell Death Dis.201910318410.1038/s41419‑019‑1439‑y 30796202
     [Google Scholar]
  31. DuG. MaR. LiH. HeJ. FengK. NiuD. YinD. Increased expression of hsa_circ_0002111 and its clinical significance in papillary thyroid cancer.Front. Oncol.20211164401110.3389/fonc.2021.644011 33718243
     [Google Scholar]
  32. ChenW. FuJ. ChenY. LiY. NingL. HuangD. YanS. ZhangQ. Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer.Aging 20211312165001651210.18632/aging.203172 34153004
     [Google Scholar]
  33. DaiL. ZhangW. WangY. YuK. LeQ. WuX. circAGTPBP1 promotes the progression of papillary thyroid cancer through the notch pathway via the miR-34a-5p/notch1 axis.iScience202326910756410.1016/j.isci.2023.107564 37622004
     [Google Scholar]
  34. LiaoJ. WeiY. LiangJ. WenJ. ChenX. ZhangB. ChuL. Insight into the structure, physiological function, and role in cancer of m6A readers—YTH domain-containing proteins.Cell Death Discov.20228113710.1038/s41420‑022‑00947‑0 35351856
     [Google Scholar]
  35. ChenY. LinY. ShuY. HeJ. GaoW. Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer.Mol. Cancer20201919410.1186/s12943‑020‑01207‑4 32443966
     [Google Scholar]
  36. HuangX. GuoH. WangL. YangL. ShaoZ. ZhangW. Recent advances in crosstalk between N6-methyladenosine (m6A) modification and circular RNAs in cancer.Mol. Ther. Nucleic Acids20222794795510.1016/j.omtn.2022.01.013 35211355
     [Google Scholar]
  37. LiuJ. YueY. HanD. WangX. FuY. ZhangL. JiaG. YuM. LuZ. DengX. DaiQ. ChenW. HeC.A. METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation.Nat. Chem. Biol.2014102939510.1038/nchembio.1432 24316715
     [Google Scholar]
  38. HeJ. ZhouM. YinJ. WanJ. ChuJ. JiaJ. ShengJ. WangC. YinH. HeF. METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration.Mol. Ther.20212951821183710.1016/j.ymthe.2021.01.019 33484966
     [Google Scholar]
  39. KastenhuberE.R. LoweS.W. Putting p53 in context.Cell201717061062107810.1016/j.cell.2017.08.028 28886379
     [Google Scholar]
  40. HeidariZ. Harati-SadeghM. ArianA. Maruei-MilanR. SalimiS. The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features.IUBMB Life202072592293010.1002/iub.2225 31895498
     [Google Scholar]
  41. RodriguesM.G. da SilvaL.F.F. Araujo-FilhoV.J.F. MoscaL.M. Araujo-NetoV.J.F. KowalskiL.P. CarneiroP.C. Incidental thyroid carcinoma: Correlation between FNAB cytology and pathological examination in 1093 cases.Clinics 20227710002210.1016/j.clinsp.2022.100022 35306374
     [Google Scholar]
  42. HoA.S. SartiE.E. JainK.S. WangH. NixonI.J. ShahaA.R. ShahJ.P. KrausD.H. GhosseinR. FishS.A. WongR.J. LinO. MorrisL.G.T. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS).Thyroid201424583283910.1089/thy.2013.0317 24341462
     [Google Scholar]
  43. GiuffridaD. GiuffridaR. PuliafitoI. VellaV. MemeoL. PuglisiC. RegalbutoC. PellegritiG. ForteS. BelfioreA. Thyroidectomy as treatment of choice for differentiated thyroid cancer.Int. J. Surg. Oncol.201920191710.1155/2019/2715260 31737363
     [Google Scholar]
  44. MulitaF. VerrasG.I. DafnomiliV.D. TchabashviliL. PerdikarisI. BousisD. LiolisE. SamarasA. VafeiadisV. DelisA. anagiotopoulos, I.; Filis, D.; Perdikaris, P.; Maroulis, I.; Anesidis, S.; Bouchagier, K. Thyroidectomy for the management of differentiated thyroid carcinoma and their outcome on early postoperative complications: A 6-year single-centre retrospective study.Chirurgia2022117555656210.21614/chirurgia.2736 36318685
     [Google Scholar]
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METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway
Endocr Metab Immune Disord Drug Targets 25, 492 (2025); https://doi.org/10.2174/0118715303290063240530053252
/content/journals/emiddt/10.2174/0118715303290063240530053252
/content/journals/emiddt/10.2174/0118715303290063240530053252
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  • Article Type:     Research Article
Keyword(s): hsa_circ_0131922; m6A modification; METTL3; p21; p53; papillary thyroid cancer

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