Page 118 - Read Online

Review

Human telomerase disease mutants and its relation with

hepatocarcinoma

2
Yin-Nan Chen , Yan-Min Zhang 1
1 School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi’an 710061, Shaanxi, China.
2 School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.

ABSTRACT
Telomerase is a special reverse transcriptase, which adds telomeric DNA repeats to the ends of chromosome to offset loss.
A vast majority of cancer cells have been shown that their telomerase was up-regulated and sustain proliferation and growth.
Hepatocellular carcinoma (HCC) is one of the most commonly occurring cancers worldwide. It is also one of the leading causes
of cancer death, and is connected with abnormal telomerase function. However, reports about the telomerase mutations and
HCC are still insufficient. In this review, the structure and mechanism of action of telomerase, inherited disorders caused by its
mutations, hepatocarcinoma, and drug development targeting telomerase are reviewed. However, further investigations are
needed to elucidate human telomerase RNA gene regulation for initiation and progression of the liver cancer.

Key words: Telomerase; mutants; hepatocarcinoma; target

Address for correspondence:
Prof. Yan-Min Zhang, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi’an 710061, Shaanxi, China.
E-mail: zhang2008@mail.xjtu.edu.cn
Received: 06-10-2015, Accepted: 28-01-2016

[8]
INTRODUCTION causes of cancer death especially in Asia and Africa. HCC
is induced by the well known risk factors such as hepatitis
Following genome duplication, eukaryotic chromosomes B, hepatitis C virus infection as well as cirrhosis. In
[8,9]
shrink due to the incomplete replication. The end of the general, it is widely accepted that telomeric shortening is
[1]
chromosomes is capped by DNA-protein complex known as responsible for limiting the life of human somatic cells and
telomere. The progressive loss of telomeric DNA threatens the expression of telomerase in the cells is sufficient to
genome stability and limits cell division. Telomerase is overcome both replication as well as senescence. Although
[2]
[10]
a special reverse transcriptase which adds telomeric DNA the mechanism involved in telomerase regulation has not
repeats to the chromosome ends to offset loss. In human, been completely understood, most types of cancer cells
[3]
telomerase is inactive in most of the somatic cells but not reveal a telomere length maintenance, which is responsible
stem cells and germlines. So far it has been found that a vast for their immortality. [11,12] Intact telomere signaling has been
majority of cancer cells, their telomerase is up-regulated demonstrated to be essential in the development of HCC.
in order to sustain proliferation and growth. Additionally, Similar to other types of cancers, it has been shown that
[4]
telomere mediated disorders such as dyskeratosis congenital, around 85% of human HCC specimens exhibit reactivation of
aplastic anemia and idiopathic pulmonary fibrosis have been telomerase activity. Transcriptional regulation of the hTERT
[13]
demonstrated to have telomerase mutations. [5-7] gene with frequent somatic mutations has been described
in several tumor cells including HCC. [14,15] Additionally, weak
Cancer is one of the world’s greatest disease burdens activation of telomerase has been reported during chronic
and hepatocellular carcinoma (HCC) is one of the leading
viral hepatitis or cirrhosis, which could be potential factors
Access this article online This is an open access article distributed under the terms of the Creative
Quick Response Code Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
Website: others to remix, tweak, and build upon the work non-commercially, as long as the
http://hrjournal.net/ author is credited and the new creations are licensed under the identical terms.
For reprints contact: service@oaepublish.com
DOI: How to cite this article: Chen YN, Zhang YM. Human telomerase
10.20517/2394-5079.2015.56 disease mutants and its relation with hepatocarcinoma. Hepatoma
Res 2016;2:109-13.

© 2016 Hepatoma Research | Published by OAE Publishing Inc. 109