- Li, Rui-Hua;
- Tian, Tian;
- Ge, Qi-Wei;
- He, Xin-Yu;
- Shi, Cheng-Yu;
- Li, Jun-Hong;
- Zhang, Zhen;
- Liu, Fang-Zhou;
- Sang, Ling-Jie;
- Yang, Zuo-Zhen;
- Liu, Ya-Zhuo;
- Xiong, Yan;
- Yan, Qingfeng;
- Li, Xu;
- Ju, Huai-Qiang;
- Liu, Jian;
- Wang, Liang-Jing;
- Shao, Jian-Zhong;
- Wang, Wenqi;
- Zhou, Tianhua;
- Lin, Aifu
Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).