Mutant Allele of CD44 (rs8193C>T) and Pum2 Regulatory Element as A Prognosis Factor of Prostate Neoplasms: A Case-Control and In Silico Studies

Expression 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),Pum2regulatory element as a prognosis factor of prostate neoplasms: a case-control,in silico studies in the Mazandaranprovince-Iran.

In a case-control study,CD44-rs8193C>T genotyping of the 420 prostate neoplasms (210benign prostatic hyperplasia (BPH) patients,210 prostate cancer patients),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,cell pathways were also investigated in silico methods.

Our 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,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,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.

Based 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,prediction of prostateneoplasms. However,more comprehensive studies in different populations (with various ethnicities,large populationsizes),and also CD44v6 gene expression studies in protein,transcript levels are required to confirm our data.