Abstract

BackgroundlncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. In previous studies, miR-7-5p has been found to be significantly down-regulated in mesenchymal-like lung cancer cell lines and directly regulated EGFR. In this work, we investigated the lncRNA partner of miR-7-5p in the progression of lung cancer.MethodsWe investigated the expression of miR-7-5p and the lncRNA after transfection with an miR-7-5p mimics using a microarray. The microarray results were validated using quantitative real time-polymerase Chain Reaction (qRT-PCR). The regulatory effects of lncRNA on miR-7-5p and its target were evaluated by changes in the expression of miR-7-5p after transfection with siRNAs for lncRNA and the synthesis of full-length lncRNA. The effect of miR-7-5p on lncRNA and the miRNA target was evaluated after transfection with miRNA mimic and inhibitor. The role of lncRNA in cancer progression was determined using invasion and migration assays. The level of lncRNA and EGFR in lung cancer and normal lung tissue was analyzed using TCGA data.ResultsWe found that LINC00240 was downregulated in lung cancer cell line after miR-7-5p transfection with an miR-7-5p mimic. Further investigations revealed that the knockdown of LINC00240 induced the overexpression of miR-7-5p. The overexpression of miR-7-5p diminished cancer invasion and migration. The EGFR expression was down regulated after siRNA treatment for LINC00240. Silencing LINC00240 suppressed the invasion and migration of lung cancer cells, whereas LINC00240 overexpression exerted the opposite effect. The lower expression of LINC00240 in squamous lung cancer was analyzed using TCGA data.ConclusionsTaken together, LINC00240 acted as a sponge for miR-7-5p and induced the overexpression of EGFR. LINC00240 may represent a potential target for the treatment of lung cancer.

Highlights

  • LncRNAs have important roles in regulating cancer biology

  • Expression levels of LINC00240 and Epidermal growth factor receptor (EGFR) were suppressed by miR-7-5p To identify the target genes of miR-7-5p known as a tumor suppressor, we first investigated its expression levels in 11 non-small cell lung cancer (NSCLC) cell lines (Fig. 1a)

  • In the differentially expressed genes, we focused on EGFR and LINC00240 because EGFR known as one of the master regulators in lung cancer is direct target of miR-7-5p [16]

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Summary

Introduction

LncRNAs have important roles in regulating cancer biology. Accumulating evidence has established a link between the dysregulation of lncRNAs and microRNA in cancer progression. Studies have claimed that lncRNAs are at the center of various physiological and pathological processes associated with cell cycle progression, apoptosis during cellular development and differentiation, as well as immune system [3]. They play important roles in chromatin remodeling, transcriptional repression and post-transcriptional regulation. Recent studies revealed that some lncRNAs assumed the role of molecular sponges, a behavior akin to that of competitive endogenous RNAs (ceRNAs), through miRNAs binding sites, and subsequently repressed their inhibitory effect on their natural targets Though not fully elucidated to date, some consistent threads of evidence have emerged on the dysregulation of lncRNAs’ principal role with regard to tumorigenesis and tumor progression in various cancer types [5, 6]. A number of lncRNAs have been implicated in NSCLC initiation and development, which demonstrate their potential value as diagnostic or prognostic biomarkers and therapeutic targets for NSCLC [7, 8]

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