MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip

BACKGROUND: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS: The clinical signifi...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Li, Yan, Shi-bai, Yang, Jie, Kong, Jin-liang, Shi, Ke, Ma, Fu-chao, Huang, Lin-zhen, Luo, Jie, Yin, Shu-ya, He, Rong-quan, Hu, Xiao-hua, Chen, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945423/
https://www.ncbi.nlm.nih.gov/pubmed/31906958
http://dx.doi.org/10.1186/s12920-019-0648-7
_version_ 1783485176381177856
author Gao, Li
Yan, Shi-bai
Yang, Jie
Kong, Jin-liang
Shi, Ke
Ma, Fu-chao
Huang, Lin-zhen
Luo, Jie
Yin, Shu-ya
He, Rong-quan
Hu, Xiao-hua
Chen, Gang
author_facet Gao, Li
Yan, Shi-bai
Yang, Jie
Kong, Jin-liang
Shi, Ke
Ma, Fu-chao
Huang, Lin-zhen
Luo, Jie
Yin, Shu-ya
He, Rong-quan
Hu, Xiao-hua
Chen, Gang
author_sort Gao, Li
collection PubMed
description BACKGROUND: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. RESULTS: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. CONCLUSIONS: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9.
format Online
Article
Text
id pubmed-6945423
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-69454232020-01-09 MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip Gao, Li Yan, Shi-bai Yang, Jie Kong, Jin-liang Shi, Ke Ma, Fu-chao Huang, Lin-zhen Luo, Jie Yin, Shu-ya He, Rong-quan Hu, Xiao-hua Chen, Gang BMC Med Genomics Research Article BACKGROUND: MiR-182-5p, a cancer-related microRNA (miRNA), modulates tumorigenesis and patient outcomes in various human malignances. This study interroted the clinicopathological significance and molecular mechanisms of miR-182-5p in non-small cell lung cancer (NSCLC). METHODS: The clinical significance of miR-182-5p in NSCLC subtypes was determined based on an analysis of 124 samples (lung adenocarcinomas [LUADs], n = 101; lung squamous cell carcinomas [LUSCs], n = 23) obtained from NSCLC patients and paired noncancer tissues and an analysis of data obtained from public miRNA-seq database, miRNA-chip database, and the scientific literature. The NSCLC samples (n = 124) were analyzed using the real-time quantitative polymerase chain reaction (RT-qPCR). Potential targets of miR-182-5p were identified using lists generated by miRWalk v.2.0, a comprehensive atlas of predicted and validated targets of miRNA-target interactions. Molecular events of miR-182-5p in NSCLC were unveiled based on a functional analysis of candidate targets. The association of miR-182-5p with one of the candidate target genes, homeobox A9 (HOXA9), was validated using in-house RT-qPCR and dual-luciferase reporter assays. RESULTS: The results of the in-house RT-qPCR assays analysis of data obtained from public miRNA-seq databases, miRNA-chip databases, and the scientific literature all supported upregulation of the expression level of miR-182-5p level in NSCLC. Moreover, the in-house RT-qPCR data supported the influence of upregulated miR-182-5p on malignant progression of NSCLC. In total, 774 prospective targets of miR-182-5p were identified. These targets were mainly clustered in pathways associated with biological processes, such as axonogenesis, axonal development, and Ras protein signal transduction, as well as pathways involved in axonal guidance, melanogenesis, and longevity regulation, in multiple species. Correlation analysis of the in-house RT-qPCR data and dual-luciferase reporter assays confirmed that HOXA9 was a direct target of miR-182-5p in NSCLC. CONCLUSIONS: The miR-182-5p expression level was upregulated in NSCLC tissues. MiR-182-5p may exert oncogenic influence on NSCLC through regulating target genes such as HOXA9. BioMed Central 2020-01-06 /pmc/articles/PMC6945423/ /pubmed/31906958 http://dx.doi.org/10.1186/s12920-019-0648-7 Text en © The Author(s). 2020 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 Research Article
Gao, Li
Yan, Shi-bai
Yang, Jie
Kong, Jin-liang
Shi, Ke
Ma, Fu-chao
Huang, Lin-zhen
Luo, Jie
Yin, Shu-ya
He, Rong-quan
Hu, Xiao-hua
Chen, Gang
MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title_full MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title_fullStr MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title_full_unstemmed MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title_short MiR-182-5p and its target HOXA9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of RT-qPCR, miRNA-seq and miRNA-chip
title_sort mir-182-5p and its target hoxa9 in non-small cell lung cancer: a clinical and in-silico exploration with the combination of rt-qpcr, mirna-seq and mirna-chip
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945423/
https://www.ncbi.nlm.nih.gov/pubmed/31906958
http://dx.doi.org/10.1186/s12920-019-0648-7
work_keys_str_mv AT gaoli mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT yanshibai mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT yangjie mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT kongjinliang mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT shike mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT mafuchao mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT huanglinzhen mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT luojie mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT yinshuya mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT herongquan mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT huxiaohua mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip
AT chengang mir1825panditstargethoxa9innonsmallcelllungcanceraclinicalandinsilicoexplorationwiththecombinationofrtqpcrmirnaseqandmirnachip