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DNA Methylation Profiling of hTERT Gene Alongside with the Telomere Performance in Gastric Adenocarcinoma

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Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Epigenetic modification including of DNA methylation, histone acetylation, histone methylation, histon phosphorylation and non-coding RNA can impress the gene expression and genomic stability and cause different types of malignancies and also main human disorder. Conspicuously, the epigenetic alteration special DNA methylation controls telomere length, telomerase activity and also function of different genes particularly hTERT expression. Telomeres are important in increasing the lifespan, health, aging, and the development and progression of some diseases like cancer.

Methods

This review provides an assessment of the epigenetic alterations of telomeres, telomerase and repression of its catalytic subunit, hTERT and function of long non-coding RNAs such as telomeric-repeat containing RNA (TERRA) in carcinogenesis and tumorgenesis of gastric cancer.

Results

hTERT expression is essential and indispensable in telomerase activation through immortality and malignancies and also plays an important role in maintaining telomere length. Telomeres and telomerase have been implicated in regulating epigenetic factors influencing certain gene expression. Correspondingly, these changes in the sub telomere and telomere regions are affected by the shortening of telomere length and increased telomerase activity and hTERT gene expression have been observed in many cancers, remarkably in gastric cancer.

Conclusion

Epigenetic alteration and regulation of hTERT gene expression are critical in controlling telomerase activity and its expression.

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Abbreviations

GC:

Gastric cancer

HDGC:

Hereditary diffuse gastric cancer

FAP:

Familial adenomatous polyposis

DNMTs:

DNA methyltransferases

MBDs:

Methyl-CpG binding domain proteins

HMT:

Histone methyltransferases

HDMs:

Histone demethylases

HATs:

Histone acetyltransferases

HDACs:

Histone deacetylases

HDACI:

Histone deacetylation inhibitor

ROS:

Reactive oxygen species

TRF:

Telomere Restriction Fragment Assay

aTL:

Absolute telomere length

ALT:

Alternative lengthening of telomeres

TSA:

Trichostatin A

TERRA:

Telomeric repeat-containing RNA

hTERT:

Human telomerase reverse transcriptase

HP1a:

Heterochromatin protein 1

siRNA:

Small interfering RNA

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Author notes

  1. Sogand Vahidi and Shahram Agah contributed equally to this work.

Authors and Affiliations

  1. Clinical Research Development Unit of Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran

    Sogand Vahidi & Seyedeh Elham Norollahi

  2. Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran

    Shahram Agah

  3. Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran

    Ali Akbar Samadani

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  1. Sogand Vahidi
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  2. Seyedeh Elham Norollahi
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  4. Ali Akbar Samadani
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Vahidi, S., Norollahi, S.E., Agah, S. et al. DNA Methylation Profiling of hTERT Gene Alongside with the Telomere Performance in Gastric Adenocarcinoma. J Gastrointest Canc 51, 788–799 (2020). https://doi.org/10.1007/s12029-020-00427-7

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