TERRA Gene Expression in Gastric Cancer: Role of hTERT

J Gastrointest Cancer. 2021 Jun;52(2):431-447. doi: 10.1007/s12029-020-00565-y. Epub 2021 Jan 7.

Abstract

Purpose: One of the most important serious malignancies is gastric cancer (GC) with a high mortality globally. In this way, beside the environmental factors, genetic parameter has a remarkable effective fluctuation in GC. Correspondingly, telomeres are nucleoprotein structures measuring the length of telomeres and they have special potential in diagnosis of various types of cancers. Defect protection of the telomeric length initiates the instability of the genome during cancer, including gastric cancer. The most common way of maintaining telomere length is the function of the telomerase enzyme that replicates the TTAGGG to the end of the 3' chromosome.

Methods: In this review, we want to discuss the alterations of hTERT repression on the modification of TERRA gene expression in conjunction with the importance of telomere and telomerase in GC.

Results: The telomerase enzyme contains two essential components called telomerase reverse transcriptase (hTERT) and RNA telomerase (hTR, hTERC). Deregulation of hTERT plays a key role in the multistage process of tumorigenicity and anticancer drug resistance. The direct relationship between telomerase activity and hTERT has led to hTERT to be considered a key target for cancer treatment. Recent results show that telomeres are transcribed into telomeric repeat-containing RNA (TERRA) in mammalian cells and are long noncoding RNAs (lncRNAs) identified in different tissues. In addition, most chemotherapy methods have a lot of side effects on normal cells.

Conclusion: Telomere and telomerase are useful therapeutic goal. According to the main roles of hTERT in tumorigenesis, growth, migration, and cancer invasion, hTERT and regulatory mechanisms that control the expression of hTERT are attractive therapeutic targets for cancer treatment.

Keywords: Human telomerase reverse transcriptase (hTERT); Telomerase; Telomere; Telomeric repeat-containing RNA (TERRA).

Publication types

  • Review

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Epigenesis, Genetic
  • Gene Expression
  • Humans
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Telomerase
  • Telomere / metabolism
  • Transcription Factors / genetics*

Substances

  • DMRT2 protein, human
  • DNA-Binding Proteins
  • Transcription Factors
  • Telomerase