Overexpression of lncRNA EGFR‑AS1 is associated with a poor prognosis and promotes chemotherapy resistance in non‑small cell lung cancer

Abstract

Chemoresistance is one of the most important biological elements affecting the progression and prognosis of cancer. Long non-coding RNAs (lncRNAs) are important regulators and are aberrantly expressed in various types of cancer in humans, including non-small cell lung cancer (NSCLC). The present study aimed to investigate the effect of lncRNAs on NSCLC resistance to chemotherapy. The relative expression level of epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) was quantified by reverse transcription-quantitative polymerase chain reaction analysis in NSCLC tissues, paired adjacent normal tissues, patient plasma and NSCLC cell lines, and its association with prognosis was assessed by multivariate analysis. The biological functions of EGFR-AS1 in NSCLC cells were determined in vitro. It was found that EGFR-AS1 was abnormally upregulated in NSCLC tissues compared with adjacent normal lung tissues. Furthermore, patients with NSCLC with increased expression of EGFR-AS1 had a poor prognosis. EGFR-AS1 knockdown significantly inhibited NSCLC malignancy in vitro, including cell proliferation and chemoresistance. Furthermore, the expression levels of EGFR-AS1 were increased in plasma samples from patients with cisplatin-based chemotherapy resistance. Bioinformatics analysis and a luciferase reporter assay confirmed that EGFR-AS1 mediated cell proliferation and chemoresistance through directly binding to microRNA-223. Therefore, EGFR-AS1 overexpression-induced chemoresistance can contribute to poor prognosis in NSCLC.Abbreviations: lncRNA, long non-coding RNA; NSCLC, non-small cell lung cancer; EGFR-AS1, epidermal growth factor receptor antisense RNA 1; PRC2, proteasome component 2; LSD1, lysine demethylase 1A; DNMT1, DNA methyltransferase 1; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; ceRNA, competitive endogenous RNA; IGF1R, insulin-like growth factor 1 receptor; PI3K, phosphatidylinositol 3-kinase

Construction of a competing endogenous RNA network using differentially expressed lncRNAs, miRNAs and mRNAs in non‑small cell lung cancer

“…Previous studies have revealed that altered expression of lncRNAs is associated with the development and progression of human malignant tumors, including lung and liver cancer, osteosarcoma, glioblastoma and as well as other types of cancer (8–11). Furthermore, lncRNAs can act as oncogenes or tumor suppressor genes, modulating the progression of NSCLC and affecting the overall survival (OS) of NSCLC patients (12,13).…”

A Genetic Variant rs10251977 in Long Non-coding RNA EGFR-AS1 Creates a New Binding Site for miR-891b and Modulates the Expression of EGFR A/D Isoforms

“…Our study showed both miRNAs were tumor suppressors and downregulated in tumor samples. In addition to support the ceRNA function, recent studies have reported miRNA sponging activity of EGFR-AS1 47,33 and miR-891b mediated gene regulation [48][49][50] .…”

“…Using the online STITCH database, we have found that lncRNA EGFR-AS1 has a positive interaction with PTBP1 and hnRNPs, major players in alternative splicing and essential for the generation of EGFR-A isoform with both transmembrane and tyrosine kinase domain. EGFR-AS1, a lncRNA transcribed from the antisense strand of EGFR, was found to be overexpressed in several cancers 30,11,[31][32][33] . Our study observed a significant upregulation of EGFR-AS1 in oral cancer patients suggesting the oncogenic potential of this lncRNA, which is consistent with above findings.…”

LncRNA XIST acts as a microRNA-520 sponge to regulate the cisplatin resistance in NSCLC cells by mediating BAX through ceRNA network

“…And lncRNAXIST may have some functions by downregulating miRNA-144. Compared with previous studies,the present study eventually constructed ceRNA [34] network of lncRNA XIST-miRNAs-BAX. We selected top 10 hub RNAs with higher degree through the cytoHubba (Fig.…”