LINC02678 as a Novel Prognostic Marker Promotes Aggressive Non-small-cell Lung Cancer

Abstract

Non-small-cell lung carcinoma (NSCLC) is considered to be a fatal disease and characterized by a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to act as biomarkers and therapeutic targets in solid tumors. However, the expression of lncRNAs and their clinical relevance in NSCLC remain undetermined. The gene expression data profiled in The Cancer Genome Atlas and Gene Expression Omnibus (GSE81089) were employed to screen differentially expressed lncRNAs in NSCLC. LINC02678 was found to be upregulated in NSCLC and exhibited hypomethylation of the promoter region in NSCLC tissues. LINC02678 (also called RP11-336A10.5) was associated with poorer overall survival and relapse-free survival in NSCLC patients. In vitro models of gain- and loss-of-function demonstrated that LINC02678 promotes NSCLC progression by promoting NSCLC cell proliferation and cell cycle progression, as well as inducing NSCLC cell migration, invasion and epithelial-mesenchymal transition. LINC02678 was primarily located in the nucleus and could bind with the enhancer of zeste homolog 2 (EZH2). Moreover, we found that LINC02678 knockdown impaired the occupancy capacity of EZH2 and trimethylation of lysine 27 on histone 3 (H3K27me3) at the promoter region of cyclin dependent kinase inhibitor 1B (CDKN1B) and E-cadherin, as confirmed by ChIP-qPCR. A mouse transplantation model further demonstrated that LINC02678 could promote the tumorigenic and metastatic capacities of NSCLC cells. We identified LINC02678 as a tumor promoter in NSCLC, which enhanced the growth and metastasis of NSCLC cells by binding with EZH2, indicating that LINC02678 may serve as a potential biomarker for cancer diagnosis and treatment.

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

“…In recent years, large-scale omics studies have identified novel therapeutic targets for multiple cancers [37] . We found the upregulation of APE1 in NSCLC through bioinformatics analysis [38] , which is consistent with the fact that APE1 is highly expressed in many cancer types and may function as an oncogene. Likewise, we found that APE1 expressed at significantly higher levels in LUAD cell lines and tissues than in normal lung epithelial cells and para-tumor tissues.…”

APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma

“…Large-scale omics studies in recent years have identi ed novel, therapeutic targets for multiple cancers [26]. In a previous study, We had explored upregulation of APE1 in the NSCLC through bioinformatics analysis [27], which is consistent with the fact that APE1 is highly expressed in many cancer types and functions as an oncogene. Likewise, we found that APE1 was expressed at signi cantly higher levels in the LUAD cell lines and tissues compared to the normal lung epithelia cells and para-tumor tissues respectively.…”

The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases

“…This research further demonstrates that H3K27me3 binds to p65 (Rela) and RKIP (PEBP1) promoter regions by CHIP assay, but EZH2 does not directly recruit to these two promoter regions, suggesting that the inhibition of EZH2 on p65 and RKIP expression mainly depends on its methyltransferase activity ( Wen et al, 2021 ). Moreover, EZH2-mediated H3K27 methylation attenuates the expression of TIMP-2 and TIMP-3 by inducing promoter DNA methylation in prostate cancer ( Shin and Kim, 2012 ) while the silencing of E-cadherin occurs through H3K27 methylation without DNA methylation in non-small-cell lung carcinoma ( Jia et al, 2021 ). However, the regulatory mechanism of EZH2 on E-cadherin and TIMPs is still unclear in AKI and requires further study.…”