m1A Regulator TRMT10C Predicts Poorer Survival and Contributes to Malignant Behavior in Gynecological Cancers

DNA Cell Biol. 2020 Oct;39(10):1767-1778. doi: 10.1089/dna.2020.5624. Epub 2020 Aug 21.

Abstract

N1-methyladenosine (m1A) is an important post-transcriptional modification in RNA, and plays critical roles in cellular functions. However, the relationship between m1A regulators and clinical significance of gynecological cancers remains unknown. In this study, we systematically analyzed RNA-seq and clinical data from several public database. Cell proliferation and migration assays were performed to verify the function of the m1A writer TRMT10C in cancer cells. We observed genetic alterations and dysregulated expressions of m1A regulators in gynecological cancer samples. We demonstrated that several m1A regulators could serve as prognostic biomarkers for gynecological cancer patients. The high correlations among the expression of m1A, N6-methyladenosine (m6A), and 5mC regulators were also revealed. Gene set enrichment analysis indicated that the mechanism of TRMT10C in regulating tumorigenesis was related to a variety of cancer-related pathways. Moreover, silencing TRMT10C suppressed the proliferation, colony formation, and migration of ovarian cancer and cervical cancer cells. In summary, our results highlight the importance of m1A regulators in regulating oncogenesis, and indicate that targeting specific m1A regulators might be a potential therapeutic strategy for gynecological cancers.

Keywords: TRMT10C; gynecological cancers; m1A regulator; prognosis.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Movement
  • Cell Proliferation
  • Female
  • HeLa Cells
  • Humans
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • N-methyladenosine
  • Methyltransferases
  • TRMT10c protein, human
  • Adenosine