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


ABSTRACT: Hepatocellular carcinoma is a malignant disease with improved hepatic regeneration and survival, and is activated by human telomere transferase (hTERT). hTERT is expressed during early fetal development and switched off in most adult tissues, but it becomes reactivated in HCC. The exact mechanism regulating these expression changes remains unknown during HCC progress. We evaluated the relationship between hTERT expression and human kruppel-related 3 (HKR3) and cell cycle-related factors in HCC cell lines. Following transfection for hTERT knockdown and HKR3 overexpression, proteomic and transcriptomic analyses related to hTERT were performed using liquid chromatography/mass spectrometry (LC/MS) and RNA sequencing (RNAseq) in HCC cell lines. The expression levels of hTERT, HKR3, and cell cycle-related factors were measured using western blotting, and tumor growth were evaluated via cell proliferation and cell cycle assays. Transcriptomic and proteomic analyses showed that HKR3, hTERT and cyclin-dependent kinase inhibitor 2A (CDKN2A) were correlated. Up-regulation of HKR3 expression decreased hTERT and cyclin activation and suppressed the G1/S phase of the cell cycle through CDKN2A activation. Our results suggest that HKR3 induced regulation of cell cycle through hTERT inhibition and CDKN2A activation. Our results will facilitate further exploration of the pathways regulating human telomerase activity in HCC cell lines.

SUBMITTER: Choi SH 

PROVIDER: S-EPMC7066026 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Choi Sung Hoon SH   Cho Kyung Joo KJ   Yun Sung Ho SH   Jin Bora B   Lee Ha Young HY   Ro Simon W SW   Kim Do Young DY   Ahn Sang Hoon SH   Han Kwang-Hyub KH   Park Jun Yong JY  

Journal of Cancer 20200210 9


Hepatocellular carcinoma is a malignant disease with improved hepatic regeneration and survival, and is activated by human telomere transferase (hTERT). hTERT is expressed during early fetal development and switched off in most adult tissues, but it becomes reactivated in HCC. The exact mechanism regulating these expression changes remains unknown during HCC progress. We evaluated the relationship between hTERT expression and human kruppel-related 3 (HKR3) and cell cycle-related factors in HCC c  ...[more]

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