Cited 2 time in webofscience Cited 2 time in scopus

RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis

Title
RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis
Authors
Lee, Sun HeeHyeon, Do YoungYoon, Soo-HyunJeong, Ji-HakHan, Saeng-MyungJang, Ju-WonMinh Phuong NguyenChi, Xin-ZiAn, SojinHyun, Kyung-giJung, Hee-JungSong, Ji-JoonBae, Suk-ChulKim, Woo-HoHwang, DaeheeLee, You Mie
DGIST Authors
Lee, Sun Hee; Hyeon, Do Young; Yoon, Soo-Hyun; Jeong, Ji-Hak; Han, Saeng-Myung; Jang, Ju-Won; Minh Phuong Nguyen; Chi, Xin-Zi; An, Sojin; Hyun, Kyung-gi; Jung, Hee-Jung; Song, Ji-Joon; Bae, Suk-Chul; Kim, Woo-Ho; Hwang, Daehee; Lee, You Mie
Issue Date
2021-04
Citation
Cell Death and Differentiation, 28(4), 1251-1269
Type
Article
Article Type
Article
Keywords
GASTRIC-CANCERTUMOR-SUPPRESSORPROTEINGENEEXPRESSIONBINDING
ISSN
1350-9047
Abstract
Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation of RUNX3 under hypoxia is still not fully understood. Here, we demonstrate a mechanism that G9a, lysine-specific methyltransferase (KMT), modulates RUNX3 through PTM under hypoxia. Hypoxia significantly increased G9a protein level and G9a interacted with RUNX3 Runt domain, which led to increased methylation of RUNX3 at K129 and K171. This methylation inactivated transactivation activity of RUNX3 by reducing interactions with CBFβ and p300 cofactors, as well as reducing acetylation of RUNX3 by p300, which is involved in nucleocytoplasmic transport by importin-α1. G9a-mediated methylation of RUNX3 under hypoxia promotes cancer cell proliferation by increasing cell cycle or cell division, while suppresses immune response and apoptosis, thereby promoting tumor growth during early tumorigenesis. Our results demonstrate the molecular mechanism of RUNX3 inactivation by G9a-mediated methylation for cell proliferation and antiapoptosis under hypoxia, which can be a therapeutic or preventive target to control tumor growth during early tumorigenesis. © 2020, The Author(s).
URI
http://hdl.handle.net/20.500.11750/12786
DOI
10.1038/s41418-020-00647-1
Publisher
Springer Nature
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