SNP Rs12982687 Affects Binding Capacity of LncRNA UCA1 with MiR-873-5p: Involvement in Smoking-triggered Colorectal Cancer Progression

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2020 Mar 8

PMID 32143722

Citations 17

Authors

Yang Fu

Yizheng Zhang

Jinyuan Cui

Ge Yang

Sanfei Peng

Wunan Mi

Xiangya Yin

Yang Yu

Jianwu Jiang

Qi Liu

Yiyu Qin

Wen Xu

Affiliations

Soon will be listed here.

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.

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