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CD44 rs13347C>T Variants in 3'UTR and Prostate Neoplasms: A Case-control Study and Bioinformatics Approach
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Emadoddin Moudi1    , Mohammadkazem Heydari 2, Abasalt Hosseinzadeh Colagar3 |
1- Clinical Research Development Unit of Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Mazandaran, Iran.
2- Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran, Babolsar, PC: 47416-95447, Mazandaran, Iran. , Mohamadkazem_hs@yahoo.com
3- Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran, Babolsar, PC: 47416-95447, Mazandaran, Iran. |
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Abstract: (289 Views) |
| CD44, a cell-surface receptor and a key player in cellular signaling, can act as both tumor suppressor and promoter. This study aimed to investigate the association of CD44 rs13347C>T variants with prostate neoplasms, including both benign prostatic hyperplasia (BPH) and prostate cancers using a case-control and bioinformatics approach. Genomic DNA was extracted from 545 blood samples (225 BPH, 225 prostate cancers, and 95 control) and the CD44 rs13347C>T genotypes were identified using PCR-RFLP. We explored miRNA interactions using the miRNASNP-v3 database and GeneMANIA for co-expression networks. Results showed cancer patients had significantly higher PSA levels compared to both controls (p= 0.03) and BPH (p= 0.01). Additionally, digital rectal examination-positive and smoker BPH patients showed significantly the increased cancer risk (p= 0.004, p= 0.046). Prostate cancer group indicated significantly higher frequency of CD44 rs13347C>T mutant allele compared to control and BPH groups, particularly in TT and CT+TT genotypes (p < 0.05). miRNA SNP-v3 database predicted the mutant allele of CD44 rs13347C>T could lose 1 and gain 6 miRNAs for a new site created. Co-expression analysis revealed a direct interaction between CD44 and aryl hydrocarbon receptor (AHR), a gene known to be dysregulated in smokers. Furthermore, these genes alone display co-expression interactions with integrin subunit alpha 4 (ITGA4), protein plays a paradoxical role, both suppressing and promoting tumors. Based on the findings, the mutant allele of CD44 rs13347C>T may disrupt miRNA binding, which may potentially impact CD44, AHR, and ITGA4 expression in smokers, possibly contributing to prostate cancer progression. |
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| Keywords: AHR, CD44, ITGA4, microRNAs, prostate cancer |
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Full-Text [PDF 816 kb]
(94 Downloads)
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Type of Study: Original Article |
Subject:
Genetics & Disease
Received: 2024/02/28 | Accepted: 2024/04/17 | Published: 2024/04/30
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