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Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance

Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC...

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Autores principales: Xiao, Jian, Lin, Linling, Luo, Dakui, Shi, Liang, Chen, Wangwang, Fan, Hao, Li, Zengliang, Ma, Xiang, Ni, Peidong, Yang, Li, Xu, Zekuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052141/
https://www.ncbi.nlm.nih.gov/pubmed/32123162
http://dx.doi.org/10.1038/s41389-020-0215-2
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author Xiao, Jian
Lin, Linling
Luo, Dakui
Shi, Liang
Chen, Wangwang
Fan, Hao
Li, Zengliang
Ma, Xiang
Ni, Peidong
Yang, Li
Xu, Zekuan
author_facet Xiao, Jian
Lin, Linling
Luo, Dakui
Shi, Liang
Chen, Wangwang
Fan, Hao
Li, Zengliang
Ma, Xiang
Ni, Peidong
Yang, Li
Xu, Zekuan
author_sort Xiao, Jian
collection PubMed
description Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC.
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spelling pubmed-70521412020-03-05 Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance Xiao, Jian Lin, Linling Luo, Dakui Shi, Liang Chen, Wangwang Fan, Hao Li, Zengliang Ma, Xiang Ni, Peidong Yang, Li Xu, Zekuan Oncogenesis Article Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC. Nature Publishing Group UK 2020-03-02 /pmc/articles/PMC7052141/ /pubmed/32123162 http://dx.doi.org/10.1038/s41389-020-0215-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xiao, Jian
Lin, Linling
Luo, Dakui
Shi, Liang
Chen, Wangwang
Fan, Hao
Li, Zengliang
Ma, Xiang
Ni, Peidong
Yang, Li
Xu, Zekuan
Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title_full Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title_fullStr Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title_full_unstemmed Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title_short Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance
title_sort long noncoding rna trpm2-as acts as a microrna sponge of mir-612 to promote gastric cancer progression and radioresistance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052141/
https://www.ncbi.nlm.nih.gov/pubmed/32123162
http://dx.doi.org/10.1038/s41389-020-0215-2
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