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Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics

1,2,* and 2,3,*
1
School of Medicine, Shandong University, Jinan 250012, China
2
Department of Medicine, Center for Molecular Medicine (CMM) and Bioclinicum, Karolinska Institute and Karolinska University Hospital Solna, 171 64 Solna, Sweden
3
Shandong University-Karolinska Institute Collaborative Laboratory for Cancer and Stem Cell Research, Jinan 250033, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3338; https://doi.org/10.3390/ijms20133338
Received: 18 June 2019 / Revised: 1 July 2019 / Accepted: 4 July 2019 / Published: 7 July 2019
(This article belongs to the Special Issue Role of Telomeres and Telomerase in Cancer and Aging 2019)
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Abstract

Telomerase, an RNA-dependent DNA polymerase with telomerase reverse transcriptase (TERT) as the catalytic component, is silent due to the tight repression of the TERT gene in most normal human somatic cells, whereas activated only in small subsets of cells, including stem cells, activated lymphocytes, and other highly proliferative cells. In contrast, telomerase activation via TERT induction is widespread in human malignant cells, which is a prerequisite for malignant transformation. It is well established that TERT/telomerase extends telomere length, thereby conferring sustained proliferation capacity to both normal and cancerous cells. The recent evidence has also accumulated that TERT/telomerase may participate in the physiological process and oncogenesis independently of its telomere-lengthening function. For instance, TERT is shown to interact with chromatin remodeling factors and to regulate DNA methylation, through which multiple cellular functions are attained. In the present review article, we summarize the non-canonical functions of TERT with a special emphasis on its cross-talk with epigenetics: How TERT contributes to epigenetic alterations in physiological processes and cancer, and how the aberrant epigenetics in turn facilitate TERT expression and function, eventually promoting cancer either initiation or progression or both. Finally, we briefly discuss clinical implications of the TERT-related methylation. View Full-Text
Keywords: aging; cancer; epigenetics; telomerase; telomere lengthening; telomerase reverse transcriptase (TERT) aging; cancer; epigenetics; telomerase; telomere lengthening; telomerase reverse transcriptase (TERT)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yuan, X.; Xu, D. Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics. Int. J. Mol. Sci. 2019, 20, 3338.

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