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

Yanbin Sun; Jingjing Xu

doi:10.2147/OTT.S210952

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

Onco Targets Ther. 2019 Oct 2:12:8055-8062. doi: 10.2147/OTT.S210952. eCollection 2019.

Authors

Yanbin Sun¹, Jingjing Xu²

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, People's Republic of China.
² Department of Rheumatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province 110004, People's Republic of China.

Abstract

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.

Keywords: TCF-4; XIST; lncRNA; lung cancer.