Open AccessIdentification of genes involved in the regulation of TERT in hepatocellular carcinoma
Author(s) -
Amisaki Masataka,
Tsuchiya Hiroyuki,
Sakabe Tomohiko,
Fujiwara Yoshiyuki,
Shiota Goshi
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13884
Subject(s) - hepatocellular carcinoma , telomerase , gene , biology , telomerase reverse transcriptase , promoter , downregulation and upregulation , cancer research , telomere , liver cancer , gene expression , microbiology and biotechnology , cancer , transcription factor , genetics
Telomerase reverse transcriptase ( TERT ) promotes immortalization by protecting telomeres in cancer cells. 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. Regulators of TERT transcription are, therefore, predicted to be plausible targets for HCC treatment. We undertook a genome‐wide sh RNA library screen and identified C15orf55 and C7orf43 as regulators of TERT expression in HepG2 cells. Promoter assays showed that C15orf55‐ and C7orf43‐responsive sites exist between base pairs −58 and +36 and −169 and −59 in the TERT promoter, respectively. C15orf55 upregulates TERT expression by binding to two GC motifs in the SP 1 binding site of the TERT promoter. C7orf43 upregulates TERT expression through Yes‐associated protein 1. The expression levels of C15orf55 and C7orf43 also correlated with that of TERT , and were significantly increased in both HCC tissues and their adjacent non‐tumor tissues, compared to normal liver tissues from non‐ HCC patients. Analysis of 377 HCC patients in The Cancer Genome Atlas dataset showed that overall survival of patients with low levels of C15orf55 and C7orf43 expression in tumor tissues was better compared with patients with high levels of C15orf55 and/or high C7orf43 expression. These results indicate that C15orf55 and C7orf43 are involved in the incidence and progression of HCC by upregulating TERT . In conclusion, we identified C15orf55 and C7orf43 as positive regulators of TERT expression in HCC tissues. These genes are promising targets for HCC treatment.