Telomerase reverse transcriptase suppression inhibits cell proliferation and promotes cell apoptosis in hepatocellular cancer

Abstract

We aimed to investigate the role of telomerase reverse transcriptase (TERT) in hepatocellular cancer (HCC) cells. R software was used for differential expressed gene analysis. Western blot and quantitative real time polymerase chain reaction (qRT-PCR), respectively, were used to detect protein expression and mRNA level of TERT in tumor cell lines. Real-time quantitative telomeric repeat amplification protocol assay, MTT assay, colony formation assay, and flow cytometry (FCM) assay were used to analyze the telomerase activity, viability, proliferation, cell cycle progression and apoptosis of HCC cells. The proliferation ratio of HCC cells transfected with TERT-siRNA was significantly decreased compared with control group. Plate clone results suggested that the number of colonies also decreased in TERT-siRNA group. FCM results showed that more cells were arrested in G0/G1 phase and apoptosis rate increased in TERT-siRNA group compared with control group. TERT suppression inhibited cell proliferation but promoted cell cycle arrest and cell apoptosis. © 2018 IUBMB Life, 70(7):642-648, 2018.

HKR3 regulates cell cycle through the inhibition of hTERT in hepatocellular carcinoma cell lines

“…However, whether hTERT leads the cell cycle by inhibiting factors other than telomeres, including CDKN2A, has remained unknown. The current study demonstrated that hTERT expression is not limited to anti-apoptosis and tumor survival but also affects the tumor cell cycle [11,14]. We also confirmed that inhibition of hTERT induces apoptosis ( Figure S2).…”

“…Aging of natural cells through reduction of telomere causes apoptosis, or apoptosis also occurs through hTERT inhibition. Thus, over-expression of hTERT leads to the synthesis of telomeres to prevent apoptosis in most solid tumors [11]. However, whether hTERT leads the cell cycle by inhibiting factors other than telomeres, including CDKN2A, has remained unknown.…”

“…International Publisher synthesizes telomeric repeats at the ends of chromosomes and replaces end sequences that are progressively lost during each cell cycle, allowing cells to escape mortality and continue to proliferate [7,8]. Reverse transcriptase telomerase is composed of two core components, a ubiquitously expressed RNA component and a catalytic subunit, human telomerase reverse transcriptase (hTERT) [8,9], whose expression is limited to the formation of a catalytically active enzyme and the regulation of telomerase activity [10,11]. Increased telomerase activity (TA) is observed in 90% of human cancer cells [8,9]; however, telomerase activity is low or undetectable in most normal human somatic cells [9].…”

“…Since expression of hTERT is highly maintained in HCC, the expression of co-related factors involved in survival or growth by hTERT remains high [22]. As well, although the cell survival in phenomena such as regulation of apoptosis by hTERT is known [11], those involving hTERT and HKR3 remain poorly understood in HCC. Therefore, we examined the effects of hTERT knockdown and HKR3 overexpression on cell proliferation, cell apoptosis, and the cell cycle, and evaluated the relationships between hTERT expression and both HKR3 and CDKN2A in HCC cell lines.…”

The effect of Telomere Lengthening on Genetic Diseases

“…[78] In cancer cells, hTERT is over-expressed to create telomeres as a mechanism to prevent apoptosis. [11,79] However, it is still unknown if hTERT inhibits other factors to reinforce the cell cycle. Choi et al hypothesized that if hTERT is somehow regulated, an anti-tumor strategy could be developed in HCC management by using human kruppel-related 3 and factors that are involved in the cell cycle of HCC cell lines.…”