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

  • Jing Jin Department of Hematology, Shaoxing People’s Hospital, Shaoxing City, Zhejiang Province, China
  • Leihua Fu Department of Hematology, Shaoxing People’s Hospital, Shaoxing City, Zhejiang Province, China
  • Pan Hong Department of Hematology, Shaoxing People’s Hospital, Shaoxing City, Zhejiang Province, China
  • Weiying Feng Department of Hematology, Shaoxing People’s Hospital, Shaoxing City, Zhejiang Province, China

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.

Published
2023-02-22
Section
Articles