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Telomere length and ROS levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma
  • 작성일2019-05-09
  • 최종수정일2019-05-09
  • 담당부서연구기획과
  • 연락처043-719-8033
  • 870
Hepatology, 2018, 67(4), 1378─1391, DOI: https://doi.org/10.1002/hep.29604

Telomere length and ROS levels are positively associated with a high risk of mortality and recurrence in hepatocellular carcinoma

Eunkyong Ko, Hyun-Wook Seo; Guhung Jung

Abstract

    Telomeres protect chromosomal ends from deterioration and have been shown to be susceptible to shortening by reactive oxygen species (ROS)-induced damage. ROS levels increase during the progression from early to advanced hepatocellular carcinoma (HCC). An independent study found that the telomeres in most HCC tissues lengthened during carcinogenic advancement. Activated telomerase has been hypothesized to elongate telomeres during the progression of malignant HCC, but it remains unclear which signaling pathway is necessary for telomerase activation in HCC. Here, we showed using cell lines derived from human HCC that H2O2, which is a major component of ROS in living organisms, elongates telomeres by increasing telomerase activity through protein kinase B (AKT) activation. The AKT inhibitor, perifosine, decreased telomere length, cellular viability, and H2O2-mediated migration and invasion capacity in HCC cells while also inhibiting AKT activation, telomere maintenance, and tumor growth in nude mice. Advanced HCC tissues showed a positive correlation among ROS levels, phosphorylated AKT (pAKT) levels, and telomere length. Furthermore, patients with HCC tumors that have high ROS levels and long telomeres displayed poorer survival rates. These data demonstrate the significant utilities of ROS levels, pAKT levels, and telomere length for predicting a poor prognosis in patients with HCC. Taken together, AKT activation could be essential for telomere maintenance in advanced HCC tumors as well as being an important contributor to malignant HCC progression. Conclusion: We showed that H2O2 contributes to telomere elongation through AKT activation in advanced HCC, suggesting that an AKT inhibitor such as perifosine may be useful for treating patients with malignant HCC.



  • 본 연구는 질병관리본부 연구개발과제(과제번호 2018-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
  • This research was supported by a fund(code 2018-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.


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