Cell Journal (Dec 2022)
Mutant Allele of CD44 (rs8193C>T) and Pum2 Regulatory Element as A Prognosis Factor of Prostate Neoplasms: A Case-Control and In Silico Studies
Abstract
ObjectiveExpression of CD44 variant 6 (CD44v6) as a homing-associated cell adhesion molecule (HCAM), hasproved to change most cancer cells. Aim of the study is the effect of mutant allele of CD44 (rs8193C>T) and Pum2regulatory element as a prognosis factor of prostate neoplasms: a case-control and in silico studies in the Mazandaranprovince-Iran.Materials and MethodsIn a case-control study, CD44-rs8193C>T genotyping of the 420 prostate neoplasms (210benign prostatic hyperplasia (BPH) patients and 210 prostate cancer patients) and 150 healthy samples are performedby the touchdown polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. The T mutantallele effects on the mRNA structure and cell pathways were also investigated in silico methods.ResultsOur results showed that the increase of T mutant allele frequency was significantly associated with BPHcompared with prostate cancer. Furthermore, results showed TT genotype was significantly associated with BPH[odds ratio (OR)=0.572 and P=0.015], and also influenced the CD44v6 transcript secondary structure, miRNA binding,and regulatory element-binding site for Pum2 protein. Attachment of Pum2 to standard CD44 transcript may lead totranscript isoform-switching and shift-expression to a variety of CD44 isoforms, which can trigger some of the cellsignaling pathways, such as Nanog-Stat, PKC-Nanog, and PKC-Twist.ConclusionBased on this, the presence of the T mutant allele of CD44 (rs8193C>T) in the populations may createa regulatory element-binding site for Pum2. So, it could be known as a prognosis factor and prediction of prostateneoplasms. However, more comprehensive studies in different populations (with various ethnicities and large populationsizes), and also CD44v6 gene expression studies in protein and transcript levels are required to confirm our data.
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