Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4

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 hav...

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Veröffentlicht in:BioMed research international 2021, Vol.2021 (1), p.7329072
Hauptverfasser: Zhao, Lu, Cheng, Bingqing, Xiong, Jie, Ma, Dan, Liu, Xin, Wang, Li, Zhang, Xi, Wang, Jishi
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Cheng, Bingqing
Xiong, Jie
Ma, Dan
Liu, Xin
Wang, Li
Zhang, Xi
Wang, Jishi
description 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.
doi_str_mv 10.1155/2021/7329072
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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.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2021/7329072</identifier><identifier>PMID: 34712735</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Acute myeloid leukemia ; Adult ; Aged ; Analysis ; Antibodies ; Bone marrow ; Cancer cells ; Cell adhesion ; Cell Adhesion - drug effects ; Cell Adhesion - genetics ; Cell differentiation ; Cell Line, Tumor ; Cell migration ; Cell Movement - drug effects ; Cell Movement - genetics ; Cell proliferation ; Down-Regulation - drug effects ; Down-Regulation - genetics ; Enzymes ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; Gene expression ; Gene Expression Regulation, Leukemic - drug effects ; Genetic aspects ; Hospitals ; Humans ; Identification and classification ; Immunoglobulins ; Invasiveness ; Isoquinolines - pharmacology ; Laboratories ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - pathology ; Leukocytes ; Male ; Medical prognosis ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Membrane proteins ; Middle Aged ; mRNA ; Myeloid leukemia ; Neoplasm Invasiveness ; Patients ; Phosphatase ; Properties ; Protein arginine methyltransferase ; Protein-Arginine N-Methyltransferases - metabolism ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Pyrimidines - pharmacology ; Receptors ; Receptors, Immunologic - genetics ; Receptors, Immunologic - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Stem cells ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Transplants &amp; implants ; Young Adult</subject><ispartof>BioMed research international, 2021, Vol.2021 (1), p.7329072</ispartof><rights>Copyright © 2021 Lu Zhao et al.</rights><rights>COPYRIGHT 2021 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2021 Lu Zhao et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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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.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>34712735</pmid><doi>10.1155/2021/7329072</doi><orcidid>https://orcid.org/0000-0001-5043-9626</orcidid><orcidid>https://orcid.org/0000-0003-1550-989X</orcidid><orcidid>https://orcid.org/0000-0001-6298-9406</orcidid><orcidid>https://orcid.org/0000-0002-8548-2832</orcidid><orcidid>https://orcid.org/0000-0002-5568-2884</orcidid><orcidid>https://orcid.org/0000-0002-9220-7898</orcidid><orcidid>https://orcid.org/0000-0002-5107-382X</orcidid><orcidid>https://orcid.org/0000-0003-1535-8809</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acute myeloid leukemia
Adult
Aged
Analysis
Antibodies
Bone marrow
Cancer cells
Cell adhesion
Cell Adhesion - drug effects
Cell Adhesion - genetics
Cell differentiation
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell Movement - genetics
Cell proliferation
Down-Regulation - drug effects
Down-Regulation - genetics
Enzymes
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
Gene expression
Gene Expression Regulation, Leukemic - drug effects
Genetic aspects
Hospitals
Humans
Identification and classification
Immunoglobulins
Invasiveness
Isoquinolines - pharmacology
Laboratories
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - pathology
Leukocytes
Male
Medical prognosis
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane proteins
Middle Aged
mRNA
Myeloid leukemia
Neoplasm Invasiveness
Patients
Phosphatase
Properties
Protein arginine methyltransferase
Protein-Arginine N-Methyltransferases - metabolism
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Pyrimidines - pharmacology
Receptors
Receptors, Immunologic - genetics
Receptors, Immunologic - metabolism
Signal transduction
Signal Transduction - drug effects
Stem cells
TOR protein
TOR Serine-Threonine Kinases - metabolism
Transplants & implants
Young Adult
title Protein Arginine Methyltransferase 5 Promotes the Migration of AML Cells by Regulating the Expression of Leukocyte Immunoglobulin-Like Receptor B4
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T20%3A50%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Protein%20Arginine%20Methyltransferase%205%20Promotes%20the%20Migration%20of%20AML%20Cells%20by%20Regulating%20the%20Expression%20of%20Leukocyte%20Immunoglobulin-Like%20Receptor%20B4&rft.jtitle=BioMed%20research%20international&rft.au=Zhao,%20Lu&rft.date=2021&rft.volume=2021&rft.issue=1&rft.spage=7329072&rft.pages=7329072-&rft.issn=2314-6133&rft.eissn=2314-6141&rft_id=info:doi/10.1155/2021/7329072&rft_dat=%3Cgale_pubme%3EA696844222%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2589570699&rft_id=info:pmid/34712735&rft_galeid=A696844222&rfr_iscdi=true