Rs12039395 Variant Influences the Expression of hsa-miR-181a-5p and PTEN Toward Colorectal Cancer Risk.

Autor: El-Korany WA; Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt., Zahran WE; Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt., Alm El-Din MA; Clinical Oncology Department, Faculty of Medicine, Tanta University, Gharbia, Egypt., Al-Shenawy HA; Pathology Department, Faculty of Medicine, Tanta University, Gharbia, Egypt., Soliman AF; Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt. ahmed.fathi@sci.asu.edu.eg.
Jazyk: angličtina
Zdroj: Digestive diseases and sciences [Dig Dis Sci] 2024 Sep; Vol. 69 (9), pp. 3318-3332. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1007/s10620-024-08517-3
Abstrakt: Background: Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes could alter miRNA expression levels or processing and, thus, may contribute to colorectal cancer (CRC) development. Therefore, this study aimed to examine whether the MIR181A1 genomic sequence possesses SNPs that can affect the expression of hsa-miR-181a-5p and, subsequently, impact its targets and associate with CRC risk.
Methods: The NCBI dbSNP database was searched for possible SNPs associated with MIR181A1. One SNP with a minor allele frequency > 5%, rs12039395 G > T was identified. In silico analyses determined the effect of the SNP on the secondary structure of the miRNA and predicted the hsa-miR-181a-5p target genes. The SNP was genotyped using allelic discrimination assay, the relative hsa-miR-181a-5p expression level was determined using quantitative real-time PCR, and immunohistochemical staining was used to detect target genes in 192 paraffin-embedded specimens collected from 160 CRC patients and 32 healthy subjects.
Results: The rs6505162 SNP conferred protection against CRC, and the G-allele presence provides may provide accessibility for the transcriptional machinery. Hsa-miR-181a-5p was significantly over-expressed in the CRC group compared to controls and in samples carrying the G-allele compared to those with T-allele. PTEN, identified as the only hsa-miR-181a-5p target implicated in CRC, was significantly diminished in the CRC group compared to controls and showed an inverse relationship with hsa-miR-181a-5p expression level as well as negatively associated with the G-allele presence in CRC.
Conclusion: This study highlights that rs12039395 G > T may protect against CRC by influencing the expression of hsa-mir-181a-5p and its target gene, PTEN.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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