FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway

Abstract

Background: Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. Methods: qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. Results: LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8 + T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83-123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog

Integrated Characterization of lncRNA-Immune Interactions in Prostate Cancer

“…For example, lncRNA cox-2 facilitates the polarization of M2 macrophages and therefore induces the malignant phenotypes of hepatocellular carcinoma cells and angiogenesis ( Ye et al, 2018 ). As another example, FOXC1-mediated LINC00301 triggers malignant potential of non-small cell lung cancer cells and modulates the Tregs and CD8 + T cell populations by activating TGF-β signaling ( Sun C.-C. et al, 2020 ).…”

Bakkenolide‑IIIa ameliorates lipopolysaccharide‑induced inflammatory injury in human umbilical vein endothelial cells by upregulating LINC00294

“…NF-κB has also been shown to bind to the HOX antisense intergenic RNA promoter and induce its expression by 16-fold in ovarian cancer cells leading to the maintenance of DNA damage response (44). Moreover, other transcription factors, including p53 and FOXC1, have been reported to regulate lncRNA expression in a direct or indirect manner (45,46). Hence, the increased level of LINC00294 in injured-HUVECs treated with Bak-IIIa may be attributed to the potential regulatory role of NF-κB, p53 or other transcription factors.…”

Construction of a Prognostic Signature of Autophagy-Related lncRNAs in Non-Small Cell Lung Cancer

“…It is of great urgency to nd a way of predicting the overall survival rate of lung cancer. Epigenetic of genes, especially lncRNAs have shown close links to lung cancer [26][27][28]. LncRNAs as supplemental genes/ miRNAs are promising the prediction of the risk of recurrence of lung cancer.…”