m6 A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer

J Cell Physiol. 2021 Apr;236(4):2649-2658. doi: 10.1002/jcp.30023. Epub 2020 Sep 6.

Abstract

N6 -methyladenosine (m6 A) and long noncoding RNAs (lncRNAs) are both crucial regulators in non-small-cell lung cancer (NSCLC) tumorigenesis. However, the pathological roles of m6 A and lncRNAs in NSCLC progression are still limited and undefined. Here, lncRNA ABHD11-AS1 was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients. Functionally, ABHD11-AS1 promoted the proliferation and Warburg effect of NSCLC. Mechanistically, m6 A profile was analyzed by methylated RNA immunoprecipitation sequencing (MeRIP-Seq). MeRIP-Seq presented that there was m6 A modification site in ABHD11-AS1. m6 A methyltransferase-like 3 (METTL3) installed the m6 A modification and enhanced ABHD11-AS1 transcript stability to increase its expression. In conclusion, our findings highlight the function and mechanism of METTL3-induced ABHD11-AS1 in NSCLC and inspire the understanding of m6 A and lncRNA in cancer biology.

Keywords: ABHD11-AS1; METTL3; Warburg effect; non-small-cell lung cancer.

MeSH terms

  • A549 Cells
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mice
  • Middle Aged
  • RNA Stability
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Warburg Effect, Oncologic*

Substances

  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • RNA, Long Noncoding
  • Methyltransferases
  • METTL3 protein, human