LncRNA‐MALAT1 Promotes Angiogenesis of Thyroid Cancer by Modulating Tumor‐Associated Macrophage FGF2 Protein Secretion

Abstract

Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-α, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF-α and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. © 2017 Wiley Periodicals, Inc.

LncRNA TPT1‐AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression

“…However, in glioblastoma, TPT1‐AS1 was demonstrated to be a protective lncRNA, and to be highly expressed in a low risk group, through binding with inhibitory targets, including AGO2, CPSF7, ELAVL1 and FUS, predicted by CLIP‐seq data. The reason lncRNA plays opposite functions in different tumor cells may be due to the different targets it is binding to …”

“…10 The reason lncRNA plays opposite functions in different tumor cells may be due to the different targets it is binding to. [35][36][37][38] Because siRNA mainly exert their gene-silencing effects in cytoplasm, 39,40 the RNA interference in nuclei does not seem as effective as in cytoplasm. However, in some studies, siRNA were utilized to silence lncRNA and mRNA expression in the nuclei, and the downstream genes and effects were efficaciously regulated.…”

Long non‐coding RNA expressed in macrophage co‐varies with the inflammatory phenotype during macrophage development and polarization

“…Tumour‐associated macrophages (TAMs) have a particular polarization state which is deemed as M2‐like macrophage . Incubated in thyroid tumour microenvironment, macrophage showed an increased expression level of MALAT1, which mediated secretion of fibroblast growth factor‐2 (FGF2) protein, leading to decreased cytokine release, enhanced tumour neovascularization, proliferation of thyroid cancer cells and metastatic potential . In TAMs isolated from thyroid cancer, expression of lncRNA nuclear enriched abundant transcript 1 (NEAT1), which is localized in the nucleus (24), and Arg‐1 were obviously elevated, while miR‐214 was significantly decreased.…”

“…They can be activated after innate immunity receptors sensing the tissue damage and metabolic dysfunction, which is considered as the first line of defence for human immunity . In response to various stimuli, macrophages have a strong functional and phenotypic plasticity, and can be polarized to the classical M1 type and the M2 type . Toll‐like receptor (TLR) ligands, macrophage receptors with collagenous structure (MARCO) and interferon γ (IFN‐γ) may induce M1 macrophages and then promote the production of some pro‐inflammatory mediators including tumour necrosis factor‐α (TNF‐α), cytokines IL‐1, IL‐6 and IL‐23, inducible nitric oxide synthase (iNOS) and HLA‐DR .…”

The long noncoding RNA MALAT‐1 functions as a competing endogenous RNA to regulate MSL2 expression by sponging miR‐338‐3p in myasthenia gravis

“…Perturbation of ceRNA networks can lead to immune and other diseases. 24 Recent studies have reported that MALAT-1 is correlated with autoimmune diseases, including multiple myeloma, 25 SLE, 26 and diffuse large Bcell lymphoma (DLBCL). 14,15 MALAT-1 has been linked to gene regulation and alternative splicing as well as cell proliferation, apoptosis, migration, and invasion.…”