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

Document Type : Original Article

Authors

1 Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran, Babolsar, Iran

2 Department of Urology, Babol University of Medical Sciences, Babol, Iran

Abstract

Objective
Expression of CD44 variant 6 (CD44v6) as a homing-associated cell adhesion molecule (HCAM), has
proved to change most cancer cells. Aim of the study is the effect of mutant allele of CD44 (rs8193C>T) and Pum2
regulatory element as a prognosis factor of prostate neoplasms: a case-control and in silico studies in the Mazandaran
province-Iran.

Materials and Methods
In a case-control study, CD44-rs8193C>T genotyping of the 420 prostate neoplasms (210
benign prostatic hyperplasia (BPH) patients and 210 prostate cancer patients) and 150 healthy samples are performed
by the touchdown polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method. The T mutant
allele effects on the mRNA structure and cell pathways were also investigated in silico methods.

Results
Our results showed that the increase of T mutant allele frequency was significantly associated with BPH
compared 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 to
transcript isoform-switching and shift-expression to a variety of CD44 isoforms, which can trigger some of the cell
signaling pathways, such as Nanog-Stat, PKC-Nanog, and PKC-Twist.

Conclusion
Based on this, the presence of the T mutant allele of CD44 (rs8193C>T) in the populations may create
a regulatory element-binding site for Pum2. So, it could be known as a prognosis factor and prediction of prostate
neoplasms. However, more comprehensive studies in different populations (with various ethnicities and large population
sizes), and also CD44v6 gene expression studies in protein and transcript levels are required to confirm our data.

Keywords


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