A Macrophase Associated LncRNA MALR Facilitates ILF3 Liquid-liquid Phase Separation to Promote Tumor Progression
Tumor-associated macrophages (TAM) are the most abundant immune cells in tumor microenvironment. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role and the underlying mechanisms in tumor remain obscure. Here, we uncovered a Macrophage Associated LncRNA (MALR) driving LLPS of interleukin enhancer-binding factor 3 (ILF3). MALR is upregulated by TAM and associated with poor prognosis for esophageal squamous cell carcinoma (ESCC). Mechanistically, MALR facilitates malignant phenotypes of ESCC via HIF1A activation via HIF1A MALR promotes ILF3-mediated LLPS by preventing SPOP-mediated ubiquitination. Accordingly, MALR-ILF3-mediated LLPS enhances HIF1A mRNA stability by preventing PARN mediated degradation. Functionally, MALR-ILF3-HIF1A axis promotes tumor malignant progression by enhancing glycolytic activity and facilitating angiogenesis. Clinically, MALR expression significantly correlates with HIF1A pathway activation and ESCC progression.