Telomerase Reverse Transcriptase

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Jae Hyun Kwon - One of the best experts on this subject based on the ideXlab platform.

  • Correlation between Telomerase Reverse Transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma.
    Surgery, 2020
    Co-Authors: Jae Hyun Kwon
    Abstract:

    Abstract Background Telomerase Reverse Transcriptase promoter mutations were recently found to be associated with poorer prognosis in patients with papillary thyroid carcinoma. Correlation between Telomerase Reverse Transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma has not been determined. Methods Clinical information, somatic mutations, and RNA sequencing of 492 papillary thyroid carcinoma patients were obtained from The Cancer Genome Atlas. Correlations between messenger RNA expression and clinicopathologic variables were evaluated. Recursive partitioning regression trees were used to find cutoffs predicting survival. Differentially expressed gene analysis was performed by Edge-R, and Database for Annotation, Visualization and Integrated Discovery 6.7 was used to pathway analysis. Results Telomerase Reverse Transcriptase messenger RNA expression was positively correlated with stages II and IV and high MACIS Prognostic Score for Papillary Thyroid Carcinoma. Using a Telomerase Reverse Transcriptase messenger RNA level of 2.854 as a cutoff, patients with higher Telomerase Reverse Transcriptase messenger RNA expression showed poorer overall survival (hazard ratio = 20.7). The higher Telomerase Reverse Transcriptase messenger RNA group showed upregulation of 2,255 genes, with enrichment of carcinogenic pathways. Conclusion Higher Telomerase Reverse Transcriptase messenger RNA expression was associated with poorer survival in patients with papillary thyroid carcinoma and was a better predictor for death than Telomerase Reverse Transcriptase promoter mutations. Measuring Telomerase Reverse Transcriptase messenger RNA expression in thyroid cancer tissue may allow early identification of papillary thyroid carcinoma patients with worse overall survival.

Kari Hemminki - One of the best experts on this subject based on the ideXlab platform.

  • Telomerase Reverse Transcriptase promoter mutations in primary cutaneous melanoma
    Nature Communications, 2014
    Co-Authors: Barbara Heidenreich, Eduardo Nagore, Sivaramakrishna P Rachakonda, Zaida Garciacasado, Celia Requena, Victor Traves, Jurgen C Becker, N Soufir, Kari Hemminki
    Abstract:

    We previously reported a disease segregating causal germline mutation in a melanoma family and recurrent somatic mutations in metastasized tumours from unrelated patients in the core promoter region of the Telomerase Reverse Transcriptase (TERT) gene. Here we show that the TERT promoter mutations, besides causing an increased gene expression, associate with increased patient age, increased Breslow thickness and tumour ulceration in 287 primary melanomas. The mutations are more frequent at both intermittently and chronically sun-exposed sites than non-exposed sites and tend to co-occur with BRAF and CDKN2A alterations. The association with parameters generally connected with poor outcome, coupled with high recurrence and mechanistic relevance, raises the possibility of the eventual use of TERT promoter mutations in the disease management.

Yu-sheng Cong - One of the best experts on this subject based on the ideXlab platform.

  • Implications of Telomerase Reverse Transcriptase in tumor metastasis.
    BMB reports, 2020
    Co-Authors: Yongkang Zou, Yu-sheng Cong, Junzhi Zhou
    Abstract:

    Metastasis is the main culprit of the great majority of cancerrelated deaths. However, the complicated process of the invasion-metastasis cascade remains the least understood aspect of cancer biology. Telomerase plays a pivotal role in bypassing cellular senescence and sustaining the cancer progression by maintaining telomere homeostasis and genomic integrity. Telomerase Reverse Transcriptase (TERT) exerts a series of fundamental functions that are independent of its enzymatic cellular activity, including proliferation, inflammation, epithelia-mesenchymal transition (EMT), angiogenesis, DNA repair, and gene expression. Accumulating evidence indicates that TERT may facilitate most steps of the invasion-metastasis cascade. In this review, we summarize important advances that have revealed some of the mechanisms by which TERT facilitates tumor metastasis, providing an update on the non-canonical functions of Telomerase beyond telomere maintaining. [BMB Reports 2020; 53(9): 458-465].

  • Telomerase Reverse Transcriptase in the regulation of gene expression.
    BMB reports, 2014
    Co-Authors: Junzhi Zhou, Deqiang Ding, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of aging and cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Telomerase is essentially composed of an RNA component, Telomerase RNA or TERC, which serves as a template for telomeric DNA synthesis, and a catalytic subunit, Telomerase Reverse Transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats, and the maintenance of telomere length. However, accumulating evidence indicates that TERT may also have some fundamental functions that are independent of its enzymatic activity. Among these telomere-independent activities of hTERT, the role of hTERT in gene transcription has been investigated in detail. Transcriptional regulation is a fundamental process in biological systems. Several studies have shown a direct involvement of hTERT in gene transcription. This mini-review will focus on the role of hTERT in gene transcription regulation, and discuss its possible mechanisms. [BMB Reports 2014; 47(1): 8-14]

  • human Telomerase Reverse Transcriptase regulates mmp expression independently of Telomerase activity via nf κb dependent transcription
    The FASEB Journal, 2013
    Co-Authors: Deqiang Ding, Junzhi Zhou, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of aging and cancer by controlling telomere length and integrity. However, accumulating evidence indicates that Telomerase Reverse Transcriptase may have fundamental biological functions independent of its enzymatic activity in telomere maintenance. In this study, the ectopic expression of human Telomerase Reverse Transcriptase (hTERT) and its catalytic mutant hTERT K626A induced cancer cell invasion accompanied by the up-regulation of the metalloproteinases (MMPs) MMP1, -3, -9, and -10. Both hTERT and hTERT K626A induced MMP9 mRNA expression and promoter activity in an NF-κB-dependent manner. hTERT and hTERT K626A also regulated the expression of several NF-κB target genes in cancer cell lines. Furthermore, both hTERT and hTERT K626A interacted with NF-κB p65 and increased NF-κB p65 nuclear accumulation and DNA binding. A mammalian 1-hybrid assay showed a functional interplay between hTERT and NF-κB p65 that may mediate NF-κB-dependent transcription activa...

  • Implications of telomere‐independent activities of Telomerase Reverse Transcriptase in human cancer
    The FEBS journal, 2013
    Co-Authors: Deqiang Ding, Junzhi Zhou, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Experimental data from genetically modified mice and human premature aging diseases clearly indicate that intact telomere function is crucial for cell proliferation and survival, whereas dysfunctional telomeres can lead to either cancer or aging pathologies, depending on the integrity of the cellular stress response pathways. The canonical function of Telomerase Reverse Transcriptase is the synthesis of telomeric DNA repeats and the maintenance of telomere length. However, accumulating evidence indicates that Telomerase Reverse Transcriptase may also exert some fundamental biological functions independently of its enzymatic activity in telomere maintenance. More recent studies have demonstrated that Telomerase Reverse Transcriptase can act as a transcriptional modulator in the nucleus and exhibits RNA-dependent RNA polymerase activity in the mitochondria. Telomerase activation may have both telomere-dependent and telomere-independent implications for tumor progression. Many excellent reviews have described critical roles of telomere and Telomerase in human cancer; this minireview will focus on the role of Telomerase in cancer progression, with a special emphasis on the nontelomeric function of Telomerase.

Jung Hee Shin - One of the best experts on this subject based on the ideXlab platform.

  • Ultrasonographic prediction of highly aggressive Telomerase Reverse Transcriptase (TERT) promoter-mutated papillary thyroid cancer.
    Endocrine, 2017
    Co-Authors: Tae Hyuk Kim, Soo Yeon Hahn, Hye Won Jang, Sun Wook Kim, Jae Hoon Chung, Jung Hee Shin
    Abstract:

    Telomerase Reverse Transcriptase promoter mutations are found in highly aggressive thyroid malignancies. Our aim was to define the ultrasonographic features of Telomerase Reverse Transcriptase promoter-mutated papillary thyroid cancer and to evaluate their predictive performances. Ultrasonographic findings were reviewed for 185 patients with surgically confirmed papillary thyroid cancer between 1994 and 2004. Genomic DNA to identify Telomerase Reverse Transcriptase promoter mutations was extracted from archived surgical specimens. Logistic regression analysis was performed to compare clinical factors and ultrasonographic findings between Telomerase Reverse Transcriptase promoter-mutated and wild-type papillary thyroid cancers. A Telomerase Reverse Transcriptase promoter mutation was detected in 8.1% (15 of 185) of specimens from papillary thyroid cancer patients with a strong trend toward increasing age. Nonparallel orientation and microlobulated margin were independent ultrasonographic findings for predicting Telomerase Reverse Transcriptase promoter-mutated papillary thyroid cancer in patients over 50 years (odds ratio 5.898, 95% confidence interval 1.092–31.851, P = 0.039 for orientation; odds ratio 5.813, 95% confidence interval 1.320–25.602, P = 0.020 for margin). Prevalence of Telomerase Reverse Transcriptase promoter mutations increased to 50.0% in papillary thyroid cancer patients older than 50 years with both ultrasonographic findings and was 0% in patients without either finding. For identifying Telomerase Reverse Transcriptase promoter-mutated papillary thyroid cancer, ultrasonographic had 64.3% sensitivity, 80.8% specificity, 50.0% positive predictive value and 88.4% negative predictive value. Telomerase Reverse Transcriptase promoter-mutated papillary thyroid cancer could be suggested by the ultrasonographic features of nonparallel orientation and microlobulated margin in patients older than 50 years. Prebiopsy recognition of this unique ultrasonographic pattern would mandate the nodule fall into a “biopsy suggested” category.

Junzhi Zhou - One of the best experts on this subject based on the ideXlab platform.

  • Implications of Telomerase Reverse Transcriptase in tumor metastasis.
    BMB reports, 2020
    Co-Authors: Yongkang Zou, Yu-sheng Cong, Junzhi Zhou
    Abstract:

    Metastasis is the main culprit of the great majority of cancerrelated deaths. However, the complicated process of the invasion-metastasis cascade remains the least understood aspect of cancer biology. Telomerase plays a pivotal role in bypassing cellular senescence and sustaining the cancer progression by maintaining telomere homeostasis and genomic integrity. Telomerase Reverse Transcriptase (TERT) exerts a series of fundamental functions that are independent of its enzymatic cellular activity, including proliferation, inflammation, epithelia-mesenchymal transition (EMT), angiogenesis, DNA repair, and gene expression. Accumulating evidence indicates that TERT may facilitate most steps of the invasion-metastasis cascade. In this review, we summarize important advances that have revealed some of the mechanisms by which TERT facilitates tumor metastasis, providing an update on the non-canonical functions of Telomerase beyond telomere maintaining. [BMB Reports 2020; 53(9): 458-465].

  • Telomerase Reverse Transcriptase in the regulation of gene expression.
    BMB reports, 2014
    Co-Authors: Junzhi Zhou, Deqiang Ding, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of aging and cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Telomerase is essentially composed of an RNA component, Telomerase RNA or TERC, which serves as a template for telomeric DNA synthesis, and a catalytic subunit, Telomerase Reverse Transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats, and the maintenance of telomere length. However, accumulating evidence indicates that TERT may also have some fundamental functions that are independent of its enzymatic activity. Among these telomere-independent activities of hTERT, the role of hTERT in gene transcription has been investigated in detail. Transcriptional regulation is a fundamental process in biological systems. Several studies have shown a direct involvement of hTERT in gene transcription. This mini-review will focus on the role of hTERT in gene transcription regulation, and discuss its possible mechanisms. [BMB Reports 2014; 47(1): 8-14]

  • human Telomerase Reverse Transcriptase regulates mmp expression independently of Telomerase activity via nf κb dependent transcription
    The FASEB Journal, 2013
    Co-Authors: Deqiang Ding, Junzhi Zhou, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of aging and cancer by controlling telomere length and integrity. However, accumulating evidence indicates that Telomerase Reverse Transcriptase may have fundamental biological functions independent of its enzymatic activity in telomere maintenance. In this study, the ectopic expression of human Telomerase Reverse Transcriptase (hTERT) and its catalytic mutant hTERT K626A induced cancer cell invasion accompanied by the up-regulation of the metalloproteinases (MMPs) MMP1, -3, -9, and -10. Both hTERT and hTERT K626A induced MMP9 mRNA expression and promoter activity in an NF-κB-dependent manner. hTERT and hTERT K626A also regulated the expression of several NF-κB target genes in cancer cell lines. Furthermore, both hTERT and hTERT K626A interacted with NF-κB p65 and increased NF-κB p65 nuclear accumulation and DNA binding. A mammalian 1-hybrid assay showed a functional interplay between hTERT and NF-κB p65 that may mediate NF-κB-dependent transcription activa...

  • Implications of telomere‐independent activities of Telomerase Reverse Transcriptase in human cancer
    The FEBS journal, 2013
    Co-Authors: Deqiang Ding, Junzhi Zhou, Miao Wang, Yu-sheng Cong
    Abstract:

    Telomerase plays a pivotal role in the pathology of cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Experimental data from genetically modified mice and human premature aging diseases clearly indicate that intact telomere function is crucial for cell proliferation and survival, whereas dysfunctional telomeres can lead to either cancer or aging pathologies, depending on the integrity of the cellular stress response pathways. The canonical function of Telomerase Reverse Transcriptase is the synthesis of telomeric DNA repeats and the maintenance of telomere length. However, accumulating evidence indicates that Telomerase Reverse Transcriptase may also exert some fundamental biological functions independently of its enzymatic activity in telomere maintenance. More recent studies have demonstrated that Telomerase Reverse Transcriptase can act as a transcriptional modulator in the nucleus and exhibits RNA-dependent RNA polymerase activity in the mitochondria. Telomerase activation may have both telomere-dependent and telomere-independent implications for tumor progression. Many excellent reviews have described critical roles of telomere and Telomerase in human cancer; this minireview will focus on the role of Telomerase in cancer progression, with a special emphasis on the nontelomeric function of Telomerase.