Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4.
Adult
Aged
Cell Adhesion
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Down-Regulation
/ drug effects
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Female
Gene Expression Regulation, Leukemic
/ drug effects
Humans
Isoquinolines
/ pharmacology
Leukemia, Myeloid, Acute
/ genetics
Male
Membrane Glycoproteins
/ genetics
Middle Aged
Neoplasm Invasiveness
Protein-Arginine N-Methyltransferases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Pyrimidines
/ pharmacology
Receptors, Immunologic
/ genetics
Signal Transduction
/ drug effects
TOR Serine-Threonine Kinases
/ metabolism
Young Adult
Journal
BioMed research international
ISSN: 2314-6141
Titre abrégé: Biomed Res Int
Pays: United States
ID NLM: 101600173
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
08
2021
accepted:
24
09
2021
entrez:
29
10
2021
pubmed:
30
10
2021
medline:
14
1
2022
Statut:
epublish
Résumé
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults with poor prognosis. Especially for AML-M5 type, due to the strong cell migration ability, the possibility of extramedullary invasion is large and widespread, which leads to poor therapeutic effect. Previous studies have found that protein arginine methyltransferase 5 (PRMT5) could promote the proliferation and differentiation of leukemic cells in AML, but its regulation on the invasive ability of AML cells remains unclear. This study was designed to explore the role of PRMT5 in regulating the invasion of AML cells and to investigate the mechanisms. Patient samples were collected for detection of PRMT5 expression level. AML cells were used for exploring the function of PRMT5. The results of clinical samples showed that the expression of PRMT5 was significantly increased in newly diagnosed and recurrent AML patients, and the expression of leukocyte immunoglobulin-like receptor B4 (LILRB4) was positively correlated with the level of PRMT5. In the cell experiment in vitro, we found that when PRMT5 was knocked down, the invasion, migration, and adhesion capacities of MV-4-11 cells and THP-1 cells were decreased, and the mRNA and protein levels of LILRB4 were also decreased. Moreover, we screened related signaling pathways and found that PRMT5 affected the expression of downstream LILRB4 by activating mTOR pathway, which in turn enhanced the invasive ability of AML cells. Taken together, PRMT5 plays an important role in the invasion of AML, which acts via regulating the expression of LILRB4. PRMT5 could act as a potential therapeutic candidate for AML.
Identifiants
pubmed: 34712735
doi: 10.1155/2021/7329072
pmc: PMC8548104
doi:
Substances chimiques
GSK3235025
0
Isoquinolines
0
LILRB4 protein, human
0
Membrane Glycoproteins
0
Pyrimidines
0
Receptors, Immunologic
0
PRMT5 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7329072Informations de copyright
Copyright © 2021 Lu Zhao et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
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