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TCF-4 Regulated lncRNA-XIST Promotes M2 Polarization Of Macrophages And Is Associated With Lung Cancer

BACKGROUND: Little is known about the biological function of long non-coding RNA X inactive specific transcript (lncRNA XIST) and its underlying mechanism in tumor-associated macrophage (TAM) polarization of lung cancer. MATERIALS AND METHODS: The expression of lncRNA XIST in macrophages was detecte...

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Detalles Bibliográficos
Autores principales: Sun, Yanbin, Xu, Jingjing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781636/
https://www.ncbi.nlm.nih.gov/pubmed/31632059
http://dx.doi.org/10.2147/OTT.S210952
Descripción
Sumario:BACKGROUND: Little is known about the biological function of long non-coding RNA X inactive specific transcript (lncRNA XIST) and its underlying mechanism in tumor-associated macrophage (TAM) polarization of lung cancer. MATERIALS AND METHODS: The expression of lncRNA XIST in macrophages was detected by RT-qPCR. The function of lncRNA XIST on IL-4-induced M2 polarization was evaluated by transfection of shRNA and RT-qPCR or Western blotting detection of M2 specific markers. Contact between T-cell-specific transcription factor 4 (TCF-4) and lncRNA XIST was verified by bioinformatics and luciferase assay. The relation between lncRNA XIST and lung cancer was determined by bioinformatics. RESULTS: The expression of lncRNA XIST in THP-1-differentiated macrophages was significantly increased in M2 macrophages than M1 (P < 0.05). lncRNA XIST downregulation suppressed the IL-4-induced M2 polarization, inducing downregulation of M2 specific markers such as IL-10, Arg-1, and CD163. However, the suppression was aborted by overexpression of TCF-4. Mechanistically, lncRNA XIST was regulated by TCF-4 through direct binding. Additionally, lung cancer conditioned macrophages exhibited high expression of lncRNA XIST and lung cancer tissues highly expressed TCF-4, indicating TCF-4 regulated lncRNA XIST closely correlated with macrophage polarization and tumor progression of lung cancer. CONCLUSION: Taken together, this study demonstrated the important role of TCF-4 regulated lncRNA XIST in regulating M2 polarization and gave a novel insight into the TAMs regulation and potential therapeutic target of lung cancer.