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SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population

BACKGROUND/AIMS: ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3′-UTR of ErbB3 to investigate the...

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Autores principales: Shi, Yaxiang, Chen, Xuan, Xi, Biao, Yu, Xiaowen, Ouyang, Jun, Han, Chunxia, Qin, Yucheng, Wu, Defeng, Shen, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599891/
https://www.ncbi.nlm.nih.gov/pubmed/28924391
http://dx.doi.org/10.1186/s12935-017-0449-z
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author Shi, Yaxiang
Chen, Xuan
Xi, Biao
Yu, Xiaowen
Ouyang, Jun
Han, Chunxia
Qin, Yucheng
Wu, Defeng
Shen, Hong
author_facet Shi, Yaxiang
Chen, Xuan
Xi, Biao
Yu, Xiaowen
Ouyang, Jun
Han, Chunxia
Qin, Yucheng
Wu, Defeng
Shen, Hong
author_sort Shi, Yaxiang
collection PubMed
description BACKGROUND/AIMS: ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3′-UTR of ErbB3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. METHODS: We performed case–control study including 851 GC patients and 799 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, the dual luciferase reporter assay, western-blot, cell proliferation and trans-well based cell invasion assay were used to investigate the effects of the SNP on ErbB3 expression. Moreover, a 5-years-overall survival and relapse free survival were investigated between different genotypes. RESULTS: We found that patients suffering from Helicobacter pylori (Hp.) infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs3202538 (G/T) in ErbB3 3′-UTR was involved in the occurrence of GC by acting as tumor risk factors. SNP rs3202538 (G/T) could be regulated by both miR-204 and miR-211 which caused an upregulation of ErbB3 in patients. Furthermore, the carriers of T genotype was related to the significantly high expression of ErbB3, and to big tumor size, poor differentiation as well as the high probability of metastasis. Both miR-211 and miR-204 can significantly decrease cell proliferation, metastasis as well as downstream AKT activation through G but not T allele of ErbB3 3′UTR. Moreover, the SNP of G/T was associated with shorter survival of post-surgery GC patients with 5 years of follow up study. CONCLUSION: In conclusion, our findings have shown that the SNP rs3202538 (G/T) in ErbB3 3′-UTR acted as promotion factors in the GC development through disrupting the regulatory role of miR-204 and miR-211 in ErbB3 expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-017-0449-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-55998912017-09-18 SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population Shi, Yaxiang Chen, Xuan Xi, Biao Yu, Xiaowen Ouyang, Jun Han, Chunxia Qin, Yucheng Wu, Defeng Shen, Hong Cancer Cell Int Primary Research BACKGROUND/AIMS: ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3′-UTR of ErbB3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. METHODS: We performed case–control study including 851 GC patients and 799 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, the dual luciferase reporter assay, western-blot, cell proliferation and trans-well based cell invasion assay were used to investigate the effects of the SNP on ErbB3 expression. Moreover, a 5-years-overall survival and relapse free survival were investigated between different genotypes. RESULTS: We found that patients suffering from Helicobacter pylori (Hp.) infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs3202538 (G/T) in ErbB3 3′-UTR was involved in the occurrence of GC by acting as tumor risk factors. SNP rs3202538 (G/T) could be regulated by both miR-204 and miR-211 which caused an upregulation of ErbB3 in patients. Furthermore, the carriers of T genotype was related to the significantly high expression of ErbB3, and to big tumor size, poor differentiation as well as the high probability of metastasis. Both miR-211 and miR-204 can significantly decrease cell proliferation, metastasis as well as downstream AKT activation through G but not T allele of ErbB3 3′UTR. Moreover, the SNP of G/T was associated with shorter survival of post-surgery GC patients with 5 years of follow up study. CONCLUSION: In conclusion, our findings have shown that the SNP rs3202538 (G/T) in ErbB3 3′-UTR acted as promotion factors in the GC development through disrupting the regulatory role of miR-204 and miR-211 in ErbB3 expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-017-0449-z) contains supplementary material, which is available to authorized users. BioMed Central 2017-09-13 /pmc/articles/PMC5599891/ /pubmed/28924391 http://dx.doi.org/10.1186/s12935-017-0449-z Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Shi, Yaxiang
Chen, Xuan
Xi, Biao
Yu, Xiaowen
Ouyang, Jun
Han, Chunxia
Qin, Yucheng
Wu, Defeng
Shen, Hong
SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title_full SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title_fullStr SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title_full_unstemmed SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title_short SNP rs3202538 in 3′UTR region of ErbB3 regulated by miR-204 and miR-211 promote gastric cancer development in Chinese population
title_sort snp rs3202538 in 3′utr region of erbb3 regulated by mir-204 and mir-211 promote gastric cancer development in chinese population
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599891/
https://www.ncbi.nlm.nih.gov/pubmed/28924391
http://dx.doi.org/10.1186/s12935-017-0449-z
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