Abstract

BackgroundEmerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained.MethodsLncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments.ResultsLncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis.ConclusionMT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC.

Highlights

  • Emerging evidence has shown that dysregulation function of long non-coding RNAs implicated in gastric cancer (GC)

  • Expressed long noncoding RNA (lncRNA) identified in microarray and Gene Expression Omnibus (GEO) database LncRNA microarray was conducted in five pairs of GC tissues and adjacent normal tissues to investigate the lncRNA expression signatures of GC

  • Metallothionein 1 J (MT1JP) was the most remarkable, we focused on lncRNA MT1JP in the further study

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Summary

Introduction

Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). High-throughput genome and transcriptome sequencing and microarrays have indicated that apart from protein-coding genes, 75% of the human genomes is transcribed into noncoding RNAs [1, 2]. LncRNAs are functionally catalogued as noncoding transcripts are more than 200 nucleotides in length, and have no potential protein-coding ability. Increasing experimental evidence supports that lncRNA functions as competitive endogenous RNA (ceRNA), which compete for microRNA (miRNA) to up-regulate the expression of a target gene. Another study has shown that lncRNA BC032469 acted as a ceRNA for miR-1207-5p to up-regulate the expression of hTERT and promoted proliferation in gastric cancer (GC) [10]

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