SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression
Abstract Background This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. Methods LncRNASNP database was firstly adopted to predict SNPs that pos...
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doaj-244ff4a5a67648caad846c0af55ab1202020-11-25T01:57:45ZengBMCCell Communication and Signaling1478-811X2020-03-0118111810.1186/s12964-020-0518-0SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progressionYang Fu0Yizheng Zhang1Jinyuan Cui2Ge Yang3Sanfei Peng4Wunan Mi5Xiangya Yin6Yang Yu7Jianwu Jiang8Qi Liu9Yiyu Qin10Wen Xu11Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou UniversityResearch Centre of Biomedical Technology, Jiangsu Vocational College of MedicineState Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyAbstract Background This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. Methods LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. Results SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05). Conclusions SNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling.http://link.springer.com/article/10.1186/s12964-020-0518-0CRClncRNA UCA1Single nucleotide polymorphismGene-environment interactionmiR-873-5pNicotine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Fu Yizheng Zhang Jinyuan Cui Ge Yang Sanfei Peng Wunan Mi Xiangya Yin Yang Yu Jianwu Jiang Qi Liu Yiyu Qin Wen Xu |
spellingShingle |
Yang Fu Yizheng Zhang Jinyuan Cui Ge Yang Sanfei Peng Wunan Mi Xiangya Yin Yang Yu Jianwu Jiang Qi Liu Yiyu Qin Wen Xu SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression Cell Communication and Signaling CRC lncRNA UCA1 Single nucleotide polymorphism Gene-environment interaction miR-873-5p Nicotine |
author_facet |
Yang Fu Yizheng Zhang Jinyuan Cui Ge Yang Sanfei Peng Wunan Mi Xiangya Yin Yang Yu Jianwu Jiang Qi Liu Yiyu Qin Wen Xu |
author_sort |
Yang Fu |
title |
SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression |
title_short |
SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression |
title_full |
SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression |
title_fullStr |
SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression |
title_full_unstemmed |
SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression |
title_sort |
snp rs12982687 affects binding capacity of lncrna uca1 with mir-873-5p: involvement in smoking-triggered colorectal cancer progression |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2020-03-01 |
description |
Abstract Background This investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures. Methods LncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised. Results SNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05). Conclusions SNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling. |
topic |
CRC lncRNA UCA1 Single nucleotide polymorphism Gene-environment interaction miR-873-5p Nicotine |
url |
http://link.springer.com/article/10.1186/s12964-020-0518-0 |
work_keys_str_mv |
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