Long non-coding RNA FENDRR regulates IFNγ-induced M1 phenotype in macrophages

Abstract

Macrophages play an essential role in host defense and display remarkable plasticity in switching between classically (pro-inflammatory—M1) and alternatively activated (anti-inflammatory—M2) phenotypes. The molecular mechanisms of macrophage polarization are not fully understood. Long non-coding RNAs (lncRNAs) with a length of > 200 nucleotides have been shown to play diverse roles in biological processes. Aberrant expression of lncRNAs is associated with a variety of pathophysiological conditions such as cancer, diabetes, cardiovascular, pulmonary diseases, and tissue fibrosis. In this study, we investigated the role of lncRNA FENDRR in human and mouse macrophage polarization. Human THP-1 monocytes were activated with phorbol-12-myristate-13-acetate (PMA) and differentiated into M1 macrophages with IFNγ or M2 macrophages with IL4. Real-time PCR analysis revealed that FENDRR was expressed 80-fold higher in M1 macrophages than that in M2 macrophages. Overexpression of FENDRR in PMA-activated THP-1 cells increased the IFNγ-induced expression of M1 markers, including IL1β and TNFα at both mRNA and protein levels. Knockdown of FENDRR had an opposite effect. Similarly, FENDRR overexpression in primary mouse bone marrow-derived macrophages increased mRNA expression of M1 markers. FENDRR overexpression increased, while FENDRR knock-down decreased, the IFNγ-induced phosphorylation of STAT1 in PMA-activated THP-1 cells. Our studies suggest that FENDRR enhances IFNγ-induced M1 macrophage polarization via the STAT1 pathway.

A Novel Signature Constructed by Immune-Related LncRNA Predicts the Immune Landscape of Colorectal Cancer

“… Liu and Du (2019) proved that FENDRR might work as a tumor suppressor gene in colon cancer by inhibiting SOX4. Also, FENDRR is closely related to immune regulation ( Munteanu et al, 2020 ; Shen et al, 2021 ). Moreover, FENDRR takes effect in different cancers, such as hepatocellular carcinoma, cholangiocarcinoma, gastric cancer, cervical cancer, breast cancer, prostate cancer, endometrial cancer, and non-small cell lung cancer ( He et al, 2018 ; Li et al, 2018 ; Qin et al, 2019 ; Yu et al, 2019 ; Zhang G. et al, 2019 ; Zhang Y.Q.…”

A Novel Prognostic Signature of Immune-related lncRNA Pairs in Lung Adenocarcinoma

“…In detail, the overexpression of FENDRR could enhance interferon γ (IFN γ) induced M1 macrophage polarization by modulating signal transducer and activator of transcription 1 (STAT1) activation pathway. 41 LncRNA LINC01116 was found to be dysregulated in various human cancers, such as glioma, prostate cancer, breast cancer, and osteosarcoma. [42][43][44][45] And recent studies also suggested that LINC01116 plays an oncogenic role in lung cancer.…”

Long Non-Coding RNA FENDRR: Gene Structure, Expression, and Biological Relevance

“…Macrophage polarization : FENDRR was identified as a positive regulator of pro-inflammatory M1 macrophage polarization via the STAT1-dependent pathway [ 78 ]. Disorders associated with macrophage polarization include fibrosis [ 79 ], cancer [ 80 ], infections [ 81 ], insulin resistance [ 82 ], atherosclerosis [ 83 ], and autoimmune disease [ 84 ].…”