Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/134914
Title: HYPOXIA- DEPENDENT ALTERATION OF 5-HYDROXYMETHYLATION LEVELS IN LIVER CANCER PROGRESSION
Authors: YOU JIA
Keywords: Hypoxia, Liver cancer, HIF1α, 5hmC
Issue Date: 12-Aug-2016
Source: YOU JIA (2016-08-12). HYPOXIA- DEPENDENT ALTERATION OF 5-HYDROXYMETHYLATION LEVELS IN LIVER CANCER PROGRESSION. ScholarBank@NUS Repository.
Abstract: Cancer cells can adapt to tumor hypoxia microenvironment by inducing hypoxia-induced factors (HIFs). However, the regulatory mechanisms underlying the HIF-mediated gene expression need to be explored further. We report that 5-hydroxymethylation (5hmC) is accumulated under hypoxia in a HIF1α-dependent manner. Moreover, HIF1α interacts physically with the 5hmC modification enzymes TET1 and TET3. 5hmC is enriched preferentially in the genomic regions adjacent to HIF1α binding sites in response to hypoxia. Therefore, our data suggest that hypoxia may remodel DNA hydroxymethylation through transactivation of HIF1α and reinforcement of HIF1α-TET1/3 interaction. In our Akt/β-catenin driven liver cancer mouse model, 5hmC level was downregulated in the early stage of liver cancer and re-established in the late stage when hypoxia pathway was activated. Depletion of Hif1α can retard the disease progression. Together, our data reveal the functional importance of HIF1α in liver cancer and would expand the current understanding of hypoxia-induced epigenetic regulation.
URI: http://scholarbank.nus.edu.sg/handle/10635/134914
Appears in Collections:Ph.D Theses (Restricted)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
01Chap YouJ.pdf14.66 MBAdobe PDF

RESTRICTED

NoneLog In
02Chap YouJ.pdf25.95 MBAdobe PDF

RESTRICTED

NoneLog In
03Chap YouJ.pdf19.35 MBAdobe PDF

RESTRICTED

NoneLog In

Page view(s)

29
checked on Jan 14, 2018

Download(s)

20
checked on Jan 14, 2018

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.