Telomerase Reverse Transcriptase (TERT) Regulation in Thyroid Cancer: A Review

• Published in: Frontiers in endocrinology (Lausanne) Vol. 11; p. 485
• Main Authors: McKelvey, Brittany A., Umbricht, Christopher B., Zeiger, Martha A.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 31-07-2020
• Subjects: copy number variation; Endocrinology; epigenetics; telomerase; TERT; thyroid cancer; transcription
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2020.00485

Telomerase reverse transcriptase (TERT)
is the catalytic subunit of the enzyme telomerase and is essential for telomerase activity. Upregulation of
TERT
expression and resulting telomerase activity occurs in the large majority of malignancies, including thyroid cancer. This upregulation results in continued cellular proliferation and avoidance of cellular senescence and cell death. In this review we will briefly introduce
TERT
and telomerase activity as it pertains to thyroid cancer and, highlight the effects of
TERT
on cancer cells. We will also explore in detail the different
TERT
regulatory strategies and how
TERT
is reactivated in thyroid cancer cells, specifically. These regulatory mechanisms include both activating single base pair
TERT
promoter mutations and epigenetic changes at the promoter, including changes in CpG methylation and histone modifications that affect chromatin structure. Further, regulation includes the allele-specific regulation of the
TERT
promoter in thyroid cancer cells harboring the
TERT
promoter mutation. These entail allele-specific transcriptional activator binding, DNA methylation, histone modifications, and mono-allelic expression of
TERT
. Lastly,
TERT
copy number alterations and alternative splicing are also implicated. Both amplifications of the
TERT
locus and increased full-length transcripts and decreased inactive and dominant negative isoforms result in active telomerase. Finally, the clinical significance of
TERT
in thyroid cancer is also reviewed.