NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc

Abstract Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5ʹ-end cap of pre-mRNAs to participate in RNA processing, tra...

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Main Authors: Sibo Meng, Yuan Xia, Mingying Li, Yuyan Wu, Dongmei Wang, Ying Zhou, Daoxin Ma, Jingjing Ye, Tao Sun, Chunyan Ji
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-35777-2
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author Sibo Meng
Yuan Xia
Mingying Li
Yuyan Wu
Dongmei Wang
Ying Zhou
Daoxin Ma
Jingjing Ye
Tao Sun
Chunyan Ji
author_facet Sibo Meng
Yuan Xia
Mingying Li
Yuyan Wu
Dongmei Wang
Ying Zhou
Daoxin Ma
Jingjing Ye
Tao Sun
Chunyan Ji
author_sort Sibo Meng
collection DOAJ
description Abstract Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5ʹ-end cap of pre-mRNAs to participate in RNA processing, transcript nuclear export and translation. Aberrant NCBP1 expression is involved in the pathogenesis of cancers, but little is known about NCBP1 in DLBCL. We proved that NCBP1 is significantly elevated in DLBCL patients and is associated with their poor prognosis. Then, we found that NCBP1 is important for the proliferation of DLBCL cells. Moreover, we verified that NCBP1 enhances the proliferation of DLBCL cells in a METTL3-dependent manner and found that NCBP1 enhances the m6A catalytic function of METTL3 by maintaining METTL3 mRNA stabilization. Mechanistically, the expression of c-MYC is regulated by NCBP1-enhanced METTL3, and the NCBP1/METTL3/m6A/c-MYC axis is important for DLBCL progression. We identified a new pathway for DLBCL progression and suggest innovative ideas for molecular targeted therapy of DLBCL.
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spelling doaj.art-9a995b32226f4c689c05ecd4485d63a22023-05-28T11:13:59ZengNature PortfolioScientific Reports2045-23222023-05-0113111110.1038/s41598-023-35777-2NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-MycSibo Meng0Yuan Xia1Mingying Li2Yuyan Wu3Dongmei Wang4Ying Zhou5Daoxin Ma6Jingjing Ye7Tao Sun8Chunyan Ji9Department of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Hematology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityAbstract Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5ʹ-end cap of pre-mRNAs to participate in RNA processing, transcript nuclear export and translation. Aberrant NCBP1 expression is involved in the pathogenesis of cancers, but little is known about NCBP1 in DLBCL. We proved that NCBP1 is significantly elevated in DLBCL patients and is associated with their poor prognosis. Then, we found that NCBP1 is important for the proliferation of DLBCL cells. Moreover, we verified that NCBP1 enhances the proliferation of DLBCL cells in a METTL3-dependent manner and found that NCBP1 enhances the m6A catalytic function of METTL3 by maintaining METTL3 mRNA stabilization. Mechanistically, the expression of c-MYC is regulated by NCBP1-enhanced METTL3, and the NCBP1/METTL3/m6A/c-MYC axis is important for DLBCL progression. We identified a new pathway for DLBCL progression and suggest innovative ideas for molecular targeted therapy of DLBCL.https://doi.org/10.1038/s41598-023-35777-2
spellingShingle Sibo Meng
Yuan Xia
Mingying Li
Yuyan Wu
Dongmei Wang
Ying Zhou
Daoxin Ma
Jingjing Ye
Tao Sun
Chunyan Ji
NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
Scientific Reports
title NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
title_full NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
title_fullStr NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
title_full_unstemmed NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
title_short NCBP1 enhanced proliferation of DLBCL cells via METTL3-mediated m6A modification of c-Myc
title_sort ncbp1 enhanced proliferation of dlbcl cells via mettl3 mediated m6a modification of c myc
url https://doi.org/10.1038/s41598-023-35777-2
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