EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non‐small cell lung carcinoma via WNT signalling pathway

Abstract

DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation‐expression‐pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta‐catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV‐939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.

Circular RNA circβ‐catenin aggravates the malignant phenotype of non‐small‐cell lung cancer via encoding a peptide

“…Therefore, we speculated that circβ-catenin-370aa, a novel peptide, circβ-catenin re- it is known that β-catenin can increase the malignant phenotype of NSCLC. 41,42,56 In summary, these results indicated that circβ-catenin encoded β-catenin-370aa to combine with GSK3β, leading to escape the degradation of β-catenin induced by GSK3β.…”

“…co‐IP results confirmed that circβ‐catenin knockdown or overexpression was able to enhance or reduce the combination between GSK3β and β‐catenin. In addition, it is known that β‐catenin can increase the malignant phenotype of NSCLC 41,42,56 …”

KIF2C is a Biomarker Correlated With Prognosis and Immunosuppressive Microenvironment in Human Tumors

“…And EXT1 may affect tumor survival by activating the Wnt signaling pathway By PPI network analysis, we found that EXT1 was associated with KIF2C. EXT1 may affect tumor survival by activating the Wnt signaling pathway ( Kong et al, 2021 ), and it has also been demonstrated that KIF2C is activated by the Wnt signaling pathway and thus can promote liver cancer progression by activating mTORC1 signaling ( Wei et al, 2020 ), so we speculate that EXT1 may influence KIF2C and thus promote tumor development.…”

“…Figure 11 shows that KIF2C interacts with genes such as CENPH, ADAM9, NDEL1, and EXT1 and is associated with biological functions such as tubulin binding, sister chromatid segregation, and MHC II antigen presentation, suggesting that KIF2C is involved in cell cycle and immune regulation. In addition, previous studies found that the KIF2C-related CENPH, EXT1, can promote tumor progression (Wu et al, 2015; Lu et al, 2017; Kong et al, 2021 ) and ADAM9 has a significant role in tumor growth, metastasis, and immune evasion (Chou et al, 2020).…”

Exploration of Dilated Cardiomyopathy for Biomarkers and Immune Microenvironment: Evidence From RNA-seq

“…EXT1 is an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Diseases associated with EXT1 include hereditary multiple exostoses, non-small cell lung carcinoma and Chondrosarcoma [32][33][34].…”