Dataset Information

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.

SUBMITTER: Nakano Y

PROVIDER: S-EPMC6910175 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Nakano Yuta Y Isobe Kazutoshi K Kobayashi Hiroshi H Kaburaki Kyohei K Isshiki Takuma T Sakamoto Susumu S Takai Yujiro Y Tochigi Naobumi N Mikami Tetsuo T Iyoda Akira A Homma Sakae S Kishi Kazuma K

International journal of oncology 20191125 1

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 aga ...[more]

PMID: 31789388

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Project description:Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. LncRNA-AL139385.1 (ENSG00000275880) is a novel lncRNA that is abnormally expressed in various cancer types including LUAD. However, the underlying biological function and potential mechanisms of AL139385.1 driving the progression of LUAD remain unclear. In this study, we investigated the role of AL139385.1 in LUAD and found that DNA hypomethylation was positively correlated with AL139385.1 expression in LUAD. Moreover, we uncover that the expression of AL139385.1 in LUAD tissues was significantly higher than that of AL139385.1 expression in adjacent normal tissues. Kaplan-Meier survival analysis showed that patients with higher AL139385.1 expression correlated with adverse overall survival and progression-free survival. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) value of AL139385.1 was 0.808. Correlation analysis showed that AL139385.1 expression was associated with immune infiltration in LUAD. We also found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of AL139385.1 significantly inhibited cell proliferation and migration abilities of LUAD. Finally, we constructed a ceRNA network that includes hsa-miR-532-5p and four mRNAs (GALNT3, CYCS, EIF5A, and ITGB4) specific to AL139385.1 in LUAD. Subsequent Kaplan-Meier survival analysis suggested that polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), cytochrome c, somatic (CYCS), eukaryotic translation initiation factor 5A (EIF5A), and integrin subunit beta 4 (ITGB4), were potential prognostic biomarkers for patients with LUAD. In conclusion, this finding provides possible mechanisms underlying the abnormal upregulation of AL139385.1 as well as a comprehensive view of the AL139385.1-mediated competing endogenous RNAs (ceRNA) network in LUAD, thereby highlighting its potential role in diagnosis and therapy.

Dataset Information

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

Publications

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

Similar Datasets

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