Clinical importance of long non‑coding RNA LINC00460 expression in EGFR‑mutant lung adenocarcinoma

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be involved in the physiological and pathological processes of tumor pathogenesis, including epithelial-mesenchymal transition (EMT). However, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance is a major challenge in the treatment of advanced and recurrent EGFR-mutant lung adenocarcinoma. An increased understanding of the underlying mechanisms would aid in the development of effective therapeutic strategies against EGFR-TKI resistance, strategies which are urgently required for clinical therapy. In this study, long non-coding RNA LINC00460 was identified as a novel marker of a poor response to EGFR-TKI and prognosis. In lung cancer cells, LINC00460 promoted EGFR-TKI resistance as a competitive decoy for miR-149-5p, thereby facilitating interleukin (IL)-6 expression and inducing EMT-like phenotypes. The knockdown or knockout of LINC00460 in gefitinib-resistant non-small cell lung cancer cells restored the response to EGFR-TKI. In addition, as compared with patients with a low LINC00460 expression in tumors, those with a high LINC00460 expression had a significantly shorter progression-free survival following gefitinib therapy, and a shorter overall survival. Therefore, LINC00460 may be a predictor of and potential therapeutic target for EGFR-TKI resistance.

LINC00460 Is a Dual Biomarker That Acts as a Predictor for Increased Prognosis in Basal-Like Breast Cancer and Potentially Regulates Immunogenic and Differentiation-Related Genes

“…Several reports show that LINC00460 is a marker for poor OS prognosis across different tumors, such as CESC ( 48 ), HNSC ( 80 ), KIRC ( 81 ), LUAD ( 49 ) and PAAD ( 82 ). In addition, we describe here that LINC00460 high expression is significantly associated with poor survival in three different tumors (GBM, LGG and SARC) but related with a favorable survival rate in BRCA, i.e.…”

Construction of a Nomogram Based on a Hypoxia-Related lncRNA Signature to Improve the Prediction of Gastric Cancer Prognosis

“…Another study showed that colorectal cancer patients with high expression of LINC00460 have a higher incidence of tumor metastasis and that this lncRNA is an independent risk factor for prognosis (Zhang et al, 2019). In EGFR-mutant lung cancer, LINC00460 promotes EGFR-TKI resistance, and patients with high LINC00460 expression who receive gefitinib therapy have a lower five-year OS rate than do patients with low LINC00460 expression (Nakano et al, 2020). Lian et al discovered that elevated expression of LINC00460 in osteosarcoma is often accompanied by distant metastasis and poor prognosis, and this lncRNA is expected to become a therapeutic target in osteosarcoma (Lian et al, 2019).…”

Long non‐coding RNAs as potential biomarkers in the prognosis and diagnosis of lung cancer: A review and target analysis

“…Nakano et al revealed that high expression of LINC00460 led to EGFR‐tyrosine kinase inhibitors resistance in lung cancer cells as a competitive decoy for miR‐149‐5p. The LINC00460 knockout or knockdown in Gefitinib‐resistant NSCLC makes cancer‐resistant cell again sensitive to EGFR‐TKI 71 . Ma et al identified that LINC00460 activates the Gefitinib‐resistance of NSCLC via EGFR by sponging miR‐769‐5p 72 .…”

“…The LINC00460 knockout or knockdown in Gefitinib-resistant NSCLC makes cancer-resistant cell again sensitive to EGFR-TKI. 71 Ma et al identified that LINC00460 activates the Gefitinib-resistance of NSCLC via EGFR by sponging miR-769-5p. 72 Yue et al suggested that overexpression of Linc00460 induced invasion and metastasis via controlling EMT expression level in NSCLC.…”