Upregulation of M6A Reader HNRNPA2B1 Associated with Poor Prognosis and Tumor Progression in Lung Adenocarcinoma

被引:5
作者
Wang, Wei [1 ,2 ]
Li, Shengwei [2 ]
机构
[1] Chongqing Univ, Chongqing Univ Three Gorges Hosp, Dept Canc Ctr, Sch Med, Chongqing 404000, Peoples R China
[2] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing, Peoples R China
关键词
lung adenocarcinoma; n6-methyladenosine; prognosis; proliferation; invasion; migration; INTERACTION NETWORKS; WEB SERVER; RNA; CANCER; M(6)A; CELLS;
D O I
10.2174/0115748928258696230925064550
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Lung cancer is the most prevalent malignancy worldwide, and lung adenocarcinoma (LUAD) accounts for a substantial proportion of all cases. N6-methyladenosine (m6A) is the most frequent post-transcriptional modification in mRNAs that also plays a role in cancer development. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is a reader of m6A modification, which can affect tumor invasion, migration, and proliferation.Objectives The purpose of this study was to explore the prognostic factors of LUAD based on m6A through bioinformatics analysis.Materials and Methods The expression levels and prognostic significance of HNRNPA2B1 in LUAD were analyzed on the basis of data extracted from the UALCAN, GEPIA, NCBI-GEO, Human Protein Atlas, STRING, miRDB, TargetScan, PROMO, Starbase, UCSC Xena browser, TIMER, and TISIDB databases. HNRNPA2B1 protein and mRNA levels in several LUAD cell lines were detected by western blotting and qRT-PCR. CCK8, wound-healing and transwell assays were performed to evaluate the proliferation, invasion, and migration abilities of LUAD cells.Results HNRNPA2B1 mRNA was found to be significantly overexpressed in LUAD tissues, and its high levels correlated with poor OS and DFS. The genes co-expressed with HNRNPA2B1 were related to mRNA production, cell cycle, and histone binding. To determine the mechanistic basis of HNRNPA2B1 in LUAD, we next predicted the microRNAs and transcription factors that were directly associated with HNRNPA2B1, as well as copy number changes. In addition, it was found that HNRNPA2B1 expression was significantly related to CD4+ T cells, neutrophils, lymphocytes, immunomodulators, and chemokines. Besides, knocking down HNRNPA2B1 in the LUAD cells led to a significant reduction in their proliferation, invasion, and migration rates in vitro.Conclusion Elevated HNRNPA2B1 is a risk factor in LUAD and portends a poor prognosis.
引用
收藏
页码:652 / 665
页数:14
相关论文
共 55 条
[1]   Predicting effective microRNA target sites in mammalian mRNAs [J].
Agarwal, Vikram ;
Bell, George W. ;
Nam, Jin-Wu ;
Bartel, David P. .
ELIFE, 2015, 4
[2]   HNRNPA2B1 Is a Mediator of m6A-Dependent Nuclear RNA Processing Events [J].
Alarcon, Claudio R. ;
Goodarzi, Hani ;
Lee, Hyeseung ;
Liu, Xuhang ;
Tavazoie, Saeed ;
Tavazoie, Sohail F. .
CELL, 2015, 162 (06) :1299-1308
[3]   THE EFFECT OF PANCREATECTOMY AND GASTROENTERECTOMY ON THE RELEASE OF SOMATOSTATIN AND VASOACTIVE INTESTINAL POLYPEPTIDE IN EXPERIMENTAL FECAL PERITONITIS [J].
ALMDAHL, SM ;
JENSSEN, TG ;
SAMDAL, FA ;
BURHOL, PG .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1988, 23 (01) :31-34
[4]   Immune Escape Mechanisms in Non Small Cell Lung Cancer [J].
Anichini, Andrea ;
Perotti, Valentina E. ;
Sgambelluri, Francesco ;
Mortarini, Roberta .
CANCERS, 2020, 12 (12) :1-20
[5]   Ribonucleoprotein HNRNPA2B1 Interacts With and Regulates Oncogenic KRAS in Pancreatic Ductal Adenocarcinoma Cells [J].
Barcelo, Carles ;
Etchin, Julia ;
Mansour, Marc R. ;
Sanda, Takaomi ;
Ginesta, Mireia M. ;
Sanchez-Arevalo Lobo, Victor J. ;
Real, Francisco X. ;
Capella, Gabriel ;
Estanyol, Josep M. ;
Jaumot, Montserrat ;
Look, A. Thomas ;
Agell, Neus .
GASTROENTEROLOGY, 2014, 147 (04) :882-U280
[6]  
Bogomolov M, 2018, Arxiv, DOI arXiv:1705.07529
[7]   CD4+ T cell help in cancer immunology and immunotherapy [J].
Borst, Jannie ;
Ahrends, Tomasz ;
Babala, Nikolina ;
Melief, Cornelis J. M. ;
Kastenmueller, Wolfgang .
NATURE REVIEWS IMMUNOLOGY, 2018, 18 (10) :635-647
[8]   miRDB: an online database for prediction of functional microRNA targets [J].
Chen, Yuhao ;
Wang, Xiaowei .
NUCLEIC ACIDS RESEARCH, 2020, 48 (D1) :D127-D131
[9]   Radiomics in predicting treatment response in non-small-cell lung cancer: current status, challenges and future perspectives [J].
Chetan, Madhurima R. ;
Gleeson, Fergus V. .
EUROPEAN RADIOLOGY, 2021, 31 (02) :1049-1058
[10]   Genomic alterations in lung adenocarcinoma [J].
Devarakonda, Siddhartha ;
Morgensztern, Daniel ;
Govindan, Ramaswamy .
LANCET ONCOLOGY, 2015, 16 (07) :E342-E351