en Genetics & Disease Genetics & Disease Original Article Original Article <span style="font-family:Tahoma;"><span style="font-size:12px;"><span style="unicode-bidi:embed"><span style="line-height:107%">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<span dir="RTL" lang="FA">.</span></span></span></span></span> AHR, CD44, ITGA4, microRNAs, prostate cancer 275 287 http://ijmcmed.org/browse.php?a_code=A-10-7899-1&slc_lang=en&sid=1 Emadoddin Moudi emoudi@mubabol.ac.ir 100319475328460033881 100319475328460033881 No Clinical Research Development Unit of Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Mazandaran, Iran. Mohammadkazem Heydari Mohamadkazem_hs@yahoo.com 100319475328460033882 100319475328460033882 Yes Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran, Babolsar, PC: 47416-95447, Mazandaran, Iran. Abasalt Hosseinzadeh Colagar acolagar@yahoo.com 100319475328460033883 100319475328460033883 No Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran, Babolsar, PC: 47416-95447, Mazandaran, Iran.