Ribosome 18S m6A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation

  • Authors:
    • Hua Huang
    • Huan Li
    • Ruining Pan
    • Sijia Wang
    • Aamir Ali Khan
    • Yue Zhao
    • Huiyu Zhu
    • Xinhui Liu
  • View Affiliations

  • Published online on: December 28, 2021     https://doi.org/10.3892/ijo.2021.5299
  • Article Number: 9
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Abstract

Methyltransferase N6‑adenosine (METTL5) is a methyltransferase that specifically catalyzes 18S rRNA N6 methylation at adenosine 1832 (m6A1832), which is located in a critical position in the decoding center, therefore suggesting its potential importance in the regulation of translation. However, the underlying mechanism of METTL5‑mediated translation regulation of specific genes and its biological functions are largely undefined. To the best of our knowledge, the present study demonstrated for the first time that METTL5 was an oncogene that promoted cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer. In addition, the oncogenic function of METTL5 may involve an increase in c‑Myc translation, as evidenced by the fact that the oncogenic effect caused by METTL5 overexpression could be abolished by c‑Myc knockdown. Notably, m6A modifications at the 5' untranslated region (5'UTR) and coding DNA sequence region (near the 5'UTR) of c‑Myc mRNA played a critical role in the specific translation regulation by METTL5. In addition, it was further demonstrated that METTL5 and its cofactor tRNA methyltransferase activator subunit 11‑2 synergistically promote pancreatic cancer progression. These findings revealed important roles for METTL5 in the development of pancreatic cancer and present the METTL5/c‑Myc axis as a novel therapeutic strategy for treatment.
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January-2022
Volume 60 Issue 1

Print ISSN: 1019-6439
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Spandidos Publications style
Huang H, Li H, Pan R, Wang S, Khan AA, Zhao Y, Zhu H and Liu X: Ribosome 18S m<sup>6</sup>A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation. Int J Oncol 60: 9, 2022
APA
Huang, H., Li, H., Pan, R., Wang, S., Khan, A.A., Zhao, Y. ... Liu, X. (2022). Ribosome 18S m<sup>6</sup>A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation. International Journal of Oncology, 60, 9. https://doi.org/10.3892/ijo.2021.5299
MLA
Huang, H., Li, H., Pan, R., Wang, S., Khan, A. A., Zhao, Y., Zhu, H., Liu, X."Ribosome 18S m<sup>6</sup>A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation". International Journal of Oncology 60.1 (2022): 9.
Chicago
Huang, H., Li, H., Pan, R., Wang, S., Khan, A. A., Zhao, Y., Zhu, H., Liu, X."Ribosome 18S m<sup>6</sup>A methyltransferase METTL5 promotes pancreatic cancer progression by modulating c‑Myc translation". International Journal of Oncology 60, no. 1 (2022): 9. https://doi.org/10.3892/ijo.2021.5299