【摘 要】
：
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 si
【机 构】
：
MOE Laboratory of Biosystem Homeostasis and Protection,College of Life Sciences,Zhejiang University,
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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.,SNH69) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e.,LATS1).
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