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 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.

Polymorphism of lncRNAs in breast cancer: Meta‐analysis shows no association with susceptibility

“…Another example was described for colorectal cancer, when SNP rs12982687 in the lncRNA UCA1 intervened in the binding capacity of UCA1 with different miRNAs, especially miR-873-5p. 56 Also, a similar process occurs in HOTAIR, where the rs2366152C variant has the potential to gain a new binding site for miR-22 in cervical cancer. 57 The interaction of lncRNAs with one or more biomolecules such as DNA, RNA or other proteins has already been described.…”

“…A single nucleotide alteration in a lncRNA target inside a miRNA binding site sequence can block the interaction with lncRNA‐miRNA and modulate the process in a cell tumor. Another example was described for colorectal cancer, when SNP rs12982687 in the lncRNA UCA1 intervened in the binding capacity of UCA1 with different miRNAs, especially miR‐873‐5p 56 . Also, a similar process occurs in HOTAIR, where the rs2366152C variant has the potential to gain a new binding site for miR‐22 in cervical cancer 57 …”

Risk SNP-induced lncRNA-SLCC1 drives colorectal cancer through activating glycolysis signaling

“… 30 In our results, the G allele of rs6695584 was associated with poorer overall survival than the A allele, suggesting that the genotype of this risk loci might serve as a predictor of the clinical outcome of CRC patients. Analogously, Fu et al 31 demonstrated that CRC patients with genotypes TT/CT of rs12982687 enjoyed a more favorable prognosis than those with homozygote C. Genetic background combined with molecular biomarkers and clinical features could construct a more accurate model for the outcome of CRC patients.…”

The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis

“…For example, tea polyphenols (TPs) can exert anti-inflammatory, anti-oxidant, or pro-oxidant effects to promote apoptosis and act at multiple levels to inhibit CRC growth and metastasis (233). Nicotine upregulates the expression of UCA1 and HIF-1a in CRC cells and promotes the proliferation and metastasis of CRC cells (234). In addition, individuals with a family history of colorectal cancer and inflammatory bowel disease are more likely to develop colorectal cancer than individuals without such a family history of these diseases (4).…”