학술논문
TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation
Document Type
article
Author
Miho M. Suzuki; Kenta Iijima; Koichi Ogami; Keiko Shinjo; Yoshiteru Murofushi; Jingqi Xie; Xuebing Wang; Yotaro Kitano; Akira Mamiya; Yuji Kibe; Tatsunori Nishimura; Fumiharu Ohka; Ryuta Saito; Shinya Sato; Junya Kobayashi; Ryoji Yao; Kanjiro Miyata; Kazunori Kataoka; Hiroshi I. Suzuki; Yutaka Kondo
Source
Nature Communications, Vol 14, Iss 1, Pp 1-20 (2023)
Subject
Language
English
ISSN
2041-1723
Abstract
Abstract Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.