MALAT-1 regulates the AML progression by promoting the m6A modification of ZEB1

Acta Biochim Pol. 2023 Feb 22;70(1):37-43. doi: 10.18388/abp.2020_6017.

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is abnormally upregulated in various human cancers. However, the role of MALAT-1 in acute myeloid leukemia (AML) remains unclear. This study investigated the expression and function of MALAT-1 in AML. MTT assay was used to determine cell viability, qRT-PCR was applied to determine the RNA levels. Western blot was performed to detect the protein expression. Flow cytometry was conducted to measure cell apoptosis. RNA pull-down assay was carried out to detect the interaction between MALAT-1 and METTL14. RNA FISH assay was performed to determine the localization of MALAT-1 and METTL14 in AML cells. Our results have revealed the key role of MEEL14 and m6A modification in AML. Besides, MALAT-1 was significantly up-regulated in AML patients. MALAT-1 knockdown inhibited the proliferation, migration and invasion of AML cells, and induced cell apoptosis; additionally, MALAT-1 binding to METTL14 promoted the m6A modification of ZEB1. Besides, ZEB1 overexpression partially reversed the effect of MALAT-1 knockdown on the cellular functions of AML cells. Taken together, MALAT-1 promoted the aggressiveness of AML through regulating m6A modification of ZEB1.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • MALAT1 long non-coding RNA, human