1. Department of Medical Genetics; Faculty of Medicine; Hormozgan University of Medical Sciences (HUMS)
Abstract
Introduction
: mrna poly(a) tails in 3'utr is important for its stability and translation. t is observed poly(a) tails is dynamic and impact the stability and translation of most eukaryotic messenger rnas and affected on micrornas in repression. in this study, it is hypothesized that this mechanism could epigenetically explain the reason of overexpressing of oncogenes proteins without any genetic alterations in proto-oncogenes in many cancers.
Methods
Proliferating non-transformed cell lines were cultured. the breast, lung and colon cancers cell lines were selected and compared to immortalized non-transformed normal epithelial cell lines and normal corresponding tissues. the genes included cyclind1, and rab10, which were expressed in all samples. cell lines were also treated with actinomycin-d for inhibition the transcription. 3'-race and sequencing was done to analyses 3'-utr length of oncogenes.
Results
It is revealed that most of the cell lines expressed a higher amount of the shorter mrna isoform (p<0.001). the shorter mrna was 1.9 times more stable than was the longer mrna. shorter mrna isoforms was more stable and typically producing 4.3-fold more protein
Conclusion
It is found that cancer cell lines often expressed mrna isoforms with shorter 3'-utr. these shorter isoforms usually resulted from alternative cleavage and polyadenylation (apa). the apa had functional consequences in such a way that shorter mrna isoforms showed loss of microrna-mediated repression.
Keywords
Poly(a)-tail shortening length; alternative cleavage and polyadenylation (apa); oncogens; epigenetic
