LINC00261 and the Adjacent Gene FOXA2 Are Epithelial Markers and Are Suppressed during Lung Cancer Tumorigenesis and Progression.

Sonam Dhamija,Sven Diederichs,Jeanette Seiler,Yogita Sharma,Andrea Becker,Ksenia Myacheva

doi:10.3390/ncrna5010002

Sonam Dhamija, Sven Diederichs + Show 4 more

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https://doi.org/10.3390/ncrna5010002

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Abstract

Lung cancer continues to be the leading cause of cancer-related deaths worldwide, with little improvement in patient survival rates in the past decade. Long non-coding RNAs (lncRNAs) are gaining importance as possible biomarkers with prognostic potential. By large-scale data mining, we identified LINC00261 as a lncRNA which was significantly downregulated in lung cancer. Low expression of LINC00261 was associated with recurrence and poor patient survival in lung adenocarcinoma. Moreover, the gene pair of LINC00261 and its neighbor FOXA2 were significantly co-regulated. LINC00261 as well as FOXA2 negatively correlated with markers for epithelial-to-mesenchymal transition (EMT) and were suppressed by the EMT inducer TGFβ. Hierarchical clustering of gene expression data from lung cancer cell lines could further verify the association of high LINC00261/FOXA2 expression to an epithelial gene signature. Furthermore, higher expression of the LINC00261/FOXA2 locus was associated with lung cancer cell lines with lower migratory capacity. All these data establish LINC00261 and FOXA2 as an epithelial-specific marker pair, downregulated during EMT and lung cancer progression, and associated with lower cell migration potential in lung cancer cells.

Highlights

Cancer is a multigenic disease and unifying principles governing the molecular mechanisms of cancer progression and metastasis are yet to be defined [1]
In search of Long non-coding RNAs (lncRNAs) relevant to lung cancer progression and metastasis, we performed large-scale data mining of the RNA-Seq data from primary lung adenocarcinoma (LUAD) obtained from The Cancer Genome Atlas (TCGA, Bethesda, MD, USA) via the TANRIC database [17]
Cancer progression is a multistep process associated with stage-specific alterations in the transcriptome leading to uncontrolled proliferation, resistance to cell death, and increased invasiveness

Summary

Introduction

Cancer is a multigenic disease and unifying principles governing the molecular mechanisms of cancer progression and metastasis are yet to be defined [1]. Large-scale gene expression profiling studies have established the molecular heterogeneity of tumors and there is a constant search for novel biomarkers with predictive value in early diagnosis, prognosis, and prediction of recurrence or progression [2,3,4,5]. Metastasis, a process by which tumor cells spread from their primary site to distant locations in the body, is a characterizing feature of aggressive tumors and constitutes the major reason for. The role of cell migration and epithelial-to-mesenchymal transition (EMT) in metastatic progression is well established [11]. A reversal of this process of EMT, referred to as MET, could be important for tumor formation at distant sites [12]. In addition to protein-coding genes constituting transcription factors and epigenetic regulators, miRNAs, and lncRNAs contribute to this process [13,14]

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