TERT promotermutations were significantly more frequent in hepatocellular carcinomas related to hepatitis C virus infection (5/6; 83.3%) compared to tumors of other etiologies (P = 0.001).
TERT protein levels were higher in HCC (n = 28) compared to normal liver tissues (n = 8) (p =0.001), but did not differ between mutated and non-mutated tumor tissues.
In summary, constitutional variants resulting in amino acid changes in the telomerase reverse transcriptase were found in a small proportion of patients with cirrhosis-associated HCC.
In this study we constructed an adenoviral vector (designated Ad/TRAIL-F/RGD) with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter, and evaluated its antitumor activity in HCC cell lines.
Telomerase reverse transcriptase (TERT), which encodes the catalytic subunit of telomerase, is highly expressed in a variety of invasive cancers, including HCC.
In this study, we pulled down and identified RBFOX3 (RNA binding protein fox-1 homolog 3) as a novel hTERT promoter-binding protein in HCC cells using biotin-streptavidin-agarose pull-down and proteomics approach, and validated it as a regulatory factor for hTERT signaling and tumor growth in HCCs.
The correlation analysis revealed a significantly negative correlation between miR-138 and telomerase reverse transcriptase (TERT) mRNA expression in HCC.
We aimed to evaluate the occurrence of telomerase reverse transcriptase (TERT) promoter mutations in the transformation of cirrhotic nodules into hepatocellular carcinoma (HCC).
Mutations of the human telomerase reverse transcriptase promoter-known to drive malignant transformation of <i>CTNNB1</i>-mutated HCA-seem to be dispensable for <i>RSPO2</i> rearranged HCA and HCC.
Mutation of the TERT promoter is one of the most common genetic alterations in hepatocellular carcinoma (HCC), indicating that TERT upregulation is a critical event in hepatocarcinogenesis.
We also identified recurrent HBV integration events (in ≥ 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue.
In conclusion, these findings showed that combination HSV1-TK/hTERT gene therapy effectively and safely inhibits HCC cell growth in vitro and in vivo and is worthy of development in clinical trials for the treatment of HCC.
These results suggest that this assay is sensitive enough to detect hTERT mRNA in serum, and that it would be applicable for early detection and diagnosis of HCC or other cancers by a quantitative method.
The analysis of the Cancer Genome Atlas (TCGA)<sup>4</sup> dataset showed that higher levels of TERT and DNMT3B expression predicted significantly shorter survival in HCC patients.
Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression.
To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC.