Tumor-suppressive role of m6A eraser proteins FTO and ALKBH5 in oral squamous cell carcinoma

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J Clin. 2024;74(3):229–63. https://doi.org/10.3322/caac.21834.

Article  Google Scholar 

Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, Kalia K, Mandoli A. Overview of oral cavity squamous cell carcinoma: risk factors, mechanisms, and diagnostics. Oral Oncol. 2021;121: 105451. https://doi.org/10.1016/j.oraloncology.2021.105451.

Article  PubMed  Google Scholar 

Chao Y, Shang J, Ji W. ALKBH5-m6A-FOXM1 signaling axis promotes proliferation and invasion of lung adenocarcinoma cells under intermittent hypoxia. Biochem Biophys Res Commun. 2020;521(2):499–506. https://doi.org/10.1016/j.bbrc.2019.10.145.

Article  CAS  PubMed  Google Scholar 

Chen M, Zhang J. miR-186-5p inhibits the progression of oral squamous cell carcinoma by targeting ITGA6 to impair the activity of the PI3K/AKT pathway. J Oral Pathol Med: Official Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2022;51(4):322–31. https://doi.org/10.1111/jop.13288.

Article  CAS  Google Scholar 

Chen R, Zhang S, Li H, Yang M, Yiwen L, Zhang X. METTL14 promotes oral squamous cell carcinoma progression by regulating the mRNA and m6A levels of CALD1. J Environ Pathol, Toxicol Oncol. 2023;42(3):71–81. https://doi.org/10.1615/JEnvironPatholToxicolOncol.2022045134.

Article  PubMed  Google Scholar 

Darwish NM, Al-Hail MKh, Mohamed Y, Al Saady R, Mohsen S, Zar A, Al-Mansoori L, Pedersen S. The role of apolipoproteins in the commonest cancers: a review. Cancers. 2023;15(23):5565. https://doi.org/10.3390/cancers15235565.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dong J, Mao J, Wu W, Qian X, Yu Z. FTO Suppresses proliferation and induces apoptosis of T98G glioblastoma cells via N6-methyladenosine modification of GSTO1. Neurochem Res. 2025;50(2):83. https://doi.org/10.1007/s11064-025-04334-w.

Article  CAS  PubMed  Google Scholar 

Du B, Zhang Y, Liang M, Du Z, Li H, Fan C, Zhang H, Jiang Y, Bi X. N6-methyladenosine (m6A) modification and its clinical relevance in cognitive dysfunctions. Aging. 2021;13(16):20716–37. https://doi.org/10.18632/aging.203457.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fang Y, Wu X, Gu Y, Shi R, Yu T, Pan Y, Zhang J, Jing X, Ma P, Shu Y. LINC00659 cooperated with ALKBH5 to accelerate gastric cancer progression by stabilising JAK1 mRNA in an m6 A-YTHDF2-dependent manner. Clin Transl Med. 2023;13(3): e1205. https://doi.org/10.1002/ctm2.1205.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fang Z, Mei W, Qu C, Lu J, Shang L, Cao F, Li F. Role of m6A writers, erasers and readers in cancer. Exp Hematol Oncol. 2022;11(1):45. https://doi.org/10.1186/s40164-022-00298-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuwei G, Sheng L, Wei X, Chen Y, Lin Y, Li Z, Li X, Yang H, Wang Y, Yang H, Shen Y. Upregulation of circGDI2 inhibits tumorigenesis by stabilizing the expression of RNA m6A demethylase FTO in oral squamous cell carcinoma. Non-coding RNA Res. 2025;10:140–52. https://doi.org/10.1016/j.ncrna.2024.08.001.

Article  CAS  Google Scholar 

Guo X, Li K, Jiang W, Hu Y, Xiao W, Huang Y, Feng Y, Pan Q, Wan R. RNA demethylase ALKBH5 prevents pancreatic cancer progression by posttranscriptional activation of PER1 in an m6A-YTHDF2-dependent manner. Mol Cancer. 2020;19(1):91. https://doi.org/10.1186/s12943-020-01158-w.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo Y, Wang Q, Wang J, Gu Y, Song P, Wang S, Qian X, Gao X. METTL3 modulates m6A modification of CDC25B and promotes head and neck squamous cell carcinoma malignant progression. Exp Hematol Oncol. 2022;11(1):14. https://doi.org/10.1186/s40164-022-00256-3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang J, Sun W, Wang Z, Lv C, Zhang T, Zhang D, Dong W, Shao L, He L, Ji X, et al. FTO suppresses glycolysis and growth of papillary thyroid cancer via decreasing stability of APOE mRNA in an N6-methyladenosine-dependent manner. J Exp Clin Cancer Res. 2022;41(1):42. https://doi.org/10.1186/s13046-022-02254-z.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang J, Yang J, Zhang Y, Lu D, Dai Y. FTO promotes cervical cancer cell proliferation, colony formation, migration and invasion via the regulation of the BMP4/Hippo/YAP1/TAZ pathway. Exp Cell Res. 2023;6: 113585. https://doi.org/10.1016/j.yexcr.2023.113585.

Article  CAS  Google Scholar 

Huang Y, Guan Y, Zhang X. METTL3-mediated maturation of miR-99a-5p promotes cell migration and invasion in oral squamous cell carcinoma by targeting ZBTB7A. Mol Biotechnol. 2023. https://doi.org/10.1007/s12033-023-00815-x.

Article  PubMed  PubMed Central  Google Scholar 

Inchingolo F, Santacroce L, Ballini A, Topi S, Dipalma G, Haxhirexha K, Bottalico L, Charitos IA. Oral cancer: a historical review. Int J Environ Res Public Health. 2020;17(9):E3168. https://doi.org/10.3390/ijerph17093168.

Article  Google Scholar 

Jayakar SK, Loudig O, Brandwein-Gensler M, Kim RS, Ow TJ, Ustun B, Harris TM, Prystowsky MB, Childs G, Segall JE, et al. Apolipoprotein E promotes invasion in oral squamous cell carcinoma. Am J Pathol. 2017;187(10):2259–72. https://doi.org/10.1016/j.ajpath.2017.06.016.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jayasree PJ, Dutta S, Karemore P, Khandelia P. Crosstalk between m6A RNA methylation and miRNA biogenesis in cancer: an unholy nexus. Mol Biotechnol. 2023. https://doi.org/10.1007/s12033-023-00921-w.

Article  PubMed  Google Scholar 

Ji F-H, Fu X-H, Li G-Q, He Q, Qiu X-G. FTO Prevents thyroid cancer progression by SLC7A11 m6A methylation in a ferroptosis-dependent manner. Front Endocrinol. 2022;13: 857765. https://doi.org/10.3389/fendo.2022.857765.

Article  Google Scholar 

Jiang X, Liu B, Nie Z, Duan L, Xiong Q, Jin Z, Yang C, Chen Y. The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021;6(1):74. https://doi.org/10.1038/s41392-020-00450-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin D, Guo J, Wu Y, Yang L, Wang X, Du J, Dai J, Chen W, Gong K, Miao S, et al. m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Mol Cancer. 2020;19(1):40. https://doi.org/10.1186/s12943-020-01161-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jin H, Ying X, Que B, Wang X, Chao Y, Zhang H, Yuan Z, Qi D, Lin S, Min W, et al. N6-methyladenosine modification of ITGA6 mRNA promotes the development and progression of bladder cancer. EBioMedicine. 2019;47:195–207. https://doi.org/10.1016/j.ebiom.2019.07.068.

Article  PubMed  PubMed Central  Google Scholar 

Jin S, Li M, Chang H, Wang R, Zhang Z, Zhang J, He Y, Ma H. The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKε/TBK1/IRF3 pathway in head and neck squamous cell carcinoma. Mol Cancer. 2022;21(1):97. https://doi.org/10.1186/s12943-022-01572-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Karthiya R, Khandelia P. m6A RNA methylation: ramifications for gene expression and human health. Mol Biotechnol. 2020;62(10):467–84. https://doi.org/10.1007/s12033-020-00269-5.

Article  CAS  PubMed  Google Scholar 

Keller L, Xu W, Wang H-X, Winblad B, Fratiglioni L, Graff C. The obesity related gene, FTO, interacts with APOE, and is associated with Alzheimer’s disease risk: a prospective cohort study. J Alzheimer’s Dis: JAD. 2011;23(3):461–9. https://doi.org/10.3233/JAD-2010-101068.

Article  CAS  PubMed  Google Scholar 

Khademi R, Malekzadeh H, Bahrami S, Saki N, Khademi R, Villa-Diaz LG. Regulation and functions of α6-Integrin (CD49f) in cancer biology. Cancers. 2023;15(13):3466. https://doi.org/10.3390/cancers15133466.

Article 

Comments (0)

No login
gif