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Telomere Length and Telomerase Activity; A Yin and Yang of Cell Senescence
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Telomere Length, TERT, and miRNA Expression.

Martha L Slattery1, Jennifer S Herrick1, Andrew J Pellatt1

  • 1Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, Utah 84108, United States of America.

Plos One
|September 15, 2016
PubMed
Summary

MicroRNAs (miRNAs) directly associate with telomere length (TL). Genetic variations in telomerase reverse transcriptase (TERT) influence miRNA expression, suggesting TERT has roles beyond telomere maintenance.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • MicroRNAs (miRNAs) are implicated in regulating telomere length (TL).
  • Telomerase reverse transcriptase (TERT) is a key player in telomere maintenance and has been linked to colorectal cancer (CRC).
  • Previous studies in CRC patients showed associations between TL, TERT, and CRC risk.

Purpose of the Study:

  • To investigate the association between miRNAs and TL.
  • To determine if genetic variations in TERT correlate with miRNA expression levels.
  • To explore the functional implications of TERT-associated miRNAs in CRC.

Main Methods:

  • Utilized data from a population-based CRC study.
  • Measured TL using quantitative PCR (qPCR).
  • Assessed miRNA expression using an Agilent platform and gene expression via RNAseq.
  • Analyzed SNP data for TERT rs2736118 and miRNA/mRNA expression in 1152 individuals.

Main Results:

  • Thirty-three miRNAs showed a direct association with TL (FDR < 0.05).
  • TERT rs2736118 was linked to differential expression of 75 miRNAs in carcinoma versus normal colonic mucosa (FDR < 0.05).
  • Genes targeted by these miRNAs are involved in significant signaling pathways, including PTEN and PI3K/AKT signaling.

Conclusions:

  • The study provides evidence for a direct role of miRNAs in regulating TL.
  • TERT genotype influences miRNA expression patterns.
  • TERT may exert non-telomere-related functions through modulation of miRNA expression, impacting key cellular signaling pathways.