HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A...

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Autores principales: Li, Kexin, Chen, Jiongyu, Lou, Xiaoying, Li, Yiling, Qian, Benheng, Xu, Danfei, Wu, Yue, Ma, Shaohui, Zhang, Donghong, Cui, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278577/
https://www.ncbi.nlm.nih.gov/pubmed/34277606
http://dx.doi.org/10.3389/fcell.2021.658642
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author Li, Kexin
Chen, Jiongyu
Lou, Xiaoying
Li, Yiling
Qian, Benheng
Xu, Danfei
Wu, Yue
Ma, Shaohui
Zhang, Donghong
Cui, Wei
author_facet Li, Kexin
Chen, Jiongyu
Lou, Xiaoying
Li, Yiling
Qian, Benheng
Xu, Danfei
Wu, Yue
Ma, Shaohui
Zhang, Donghong
Cui, Wei
author_sort Li, Kexin
collection PubMed
description N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster.
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spelling pubmed-82785772021-07-15 HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster Li, Kexin Chen, Jiongyu Lou, Xiaoying Li, Yiling Qian, Benheng Xu, Danfei Wu, Yue Ma, Shaohui Zhang, Donghong Cui, Wei Front Cell Dev Biol Cell and Developmental Biology N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster. Frontiers Media S.A. 2021-06-30 /pmc/articles/PMC8278577/ /pubmed/34277606 http://dx.doi.org/10.3389/fcell.2021.658642 Text en Copyright © 2021 Li, Chen, Lou, Li, Qian, Xu, Wu, Ma, Zhang and Cui. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Li, Kexin
Chen, Jiongyu
Lou, Xiaoying
Li, Yiling
Qian, Benheng
Xu, Danfei
Wu, Yue
Ma, Shaohui
Zhang, Donghong
Cui, Wei
HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title_full HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title_fullStr HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title_full_unstemmed HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title_short HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster
title_sort hnrnpa2b1 affects the prognosis of esophageal cancer by regulating the mir-17-92 cluster
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278577/
https://www.ncbi.nlm.nih.gov/pubmed/34277606
http://dx.doi.org/10.3389/fcell.2021.658642
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