Oligomer-mediated modulation of hTERT alternative splicing induces telomerase inhibition and cell growth decline in human prostate cancer cells

Cellular and Molecular Life Sciences : CMLS
C BrambillaNadia Zaffaroni

Abstract

The expression of telomerase in human cells is strictly controlled by multiple mechanisms including transcription and alternative splicing of telomerase reverse transcriptase (hTERT). In this study, we demonstrated the possibility of modulating the hTERT splicing pattern in DU145 human prostate carcinoma cells through the use of 2'-O-methyl-RNA phosphorothioate oligonucleotides targeting the splicing site located between intron 5 and exon 6 in the hTERT pre-mRNA. An 18-h oligonucleotide exposure induced a decrease in the full-length hTERT transcript and a concomitant increase in the alternatively spliced transcripts, which resulted in significant inhibition of telomerase catalytic activity. Moreover, exposure to the R7 oligomer (which induced the most pronounced modulation of the hTERT splicing pattern and the greatest telomerase inhibition) caused a marked reduction in DU145 cell growth and the induction of apoptosis starting 2 days after treatment. Such data support the concept that down-regulation of hTERT expression can cause short-term effects on tumour cell growth, which are telomere-shortening independent.

Citations

Sep 26, 2008·Thyroid : Official Journal of the American Thyroid Association·Yongchun WangMartha A Zeiger
Feb 1, 2006·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·J M GuoX N Zhang
Apr 23, 2014·Stem Cells and Development·Lida RadanDean Harvey Betts
Mar 21, 2013·Wiley Interdisciplinary Reviews. RNA·Mallory A HavensMichelle L Hastings
Jul 19, 2011·The American Journal of Pathology·Yongchun WangChristopher B Umbricht
Jun 1, 2005·Mechanisms of Ageing and Development·Susan E Swanberg, Mary E Delany
Jan 3, 2007·European Journal of Cell Biology·Bettina BurnworthPetra Boukamp
Mar 9, 2017·International Journal of Molecular Sciences·Xuewen LiuXin Geng
Apr 11, 2018·Journal of Experimental & Clinical Cancer Research : CR·Guihong LiHaiyan Huang
Mar 21, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Julian P Venables
Aug 7, 2009·Nature Reviews. Urology·Prabhakar RajanHing Y Leung

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.