O-linked N-acetylglucosamine transferase promotes cervical cancer tumorigenesis through human papillomaviruses E6 and E7 oncogenesopen access
- Authors
- Kim, Minjun; Kim, Yoon Sook; Kim, Hwajin; Kang, Min Young; Park, Jeongsook; Lee, Dong Hoon; Roh, Gu Seob; Kim, Hyun Joon; Kang, Sang Soo; Cho, Gyeong Jae; Park, Ji Kwon; Cho, Jin Won; Shin, Jeong Kyu; Choi, Wan Sung
- Issue Date
- Jul-2016
- Publisher
- IMPACT JOURNALS LLC
- Keywords
- O-GlcNAcylation; host cell factor 1; OGTE6 and E7
- Citation
- ONCOTARGET, v.7, no.28, pp 44596 - 44607
- Pages
- 12
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOTARGET
- Volume
- 7
- Number
- 28
- Start Page
- 44596
- End Page
- 44607
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/194380
- DOI
- 10.18632/oncotarget.10112
- ISSN
- 19492553
- Abstract
- O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) increases O-GlcNAc modification (O-GlcNAcylation), and transcriptional co-regulator host cell factor 1 (HCF-1) is one of OGT targets. High-risk Human Papillomaviruses (HPVs) encode E6 and E7 oncoproteins, which promote cervical cancer. Here, we tested whether O-GlcNAc modification of HCF-1 affects HPV E6 and E7 expressions and tumorigenesis of cervical cancer. We found that depleting OGT with OGT-specific shRNA significantly decreased levels of E6 and E7 oncoproteins, and cervical cancer tumorigenesis, while OGT overexpression greatly increased levels of E6 and E7 oncoproteins. Notably, OGT overexpression caused dose-dependent increases in the transcriptional activity of E6 and E7, and this activity was decreased when HCF-1 was depleted with HCF-1-specific siRNA. Moreover, OGT depletion reduced proliferation, invasion, and metastasis in cervical cancer cells. Further, high glucose enhanced the interaction between OGT and HCF-1, paralleling increased levels of E6 and E7 in cervical cancer cells. Most importantly, we found that reducing OGT in HeLa cells caused decreased tumor growth in vivo. These findings identify OGT as a novel cellular factor involved in E6 and E7 expressions and cervical cancer tumorigenesis, suggesting that targeting OGT in cervical cancer may have potential therapeutic benefit.
- Files in This Item
-
- Appears in
Collections - 서울 의과대학 > 서울 교육협력지원교실 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.