Abstract
Recently, circRNAs have been found to play regulatory roles in cancer. In the present study, we aimed to investigate the characteristics and effect of circLMTK2, and its potential role as a novel biomarker in cases of gastric cancer (GC). About 111 pairs of clinical tissues from patients were collected for circLMTK2 expression investigation. Afterward, the relationship of circLMTK2 expression level and clinical features, such as survival, tumor size and so on, were analyzed, along with a multivariate Cox hazards analysis. Finally, malignant biological properties, like cell viability and mobility, were explored in cell line MGC-803. We found that circLMTK2 was a stable circRNA generated from the back-spliced Exon 10 and Exon 11 of the LMTK2 gene in GC cells. CircLMTK2 expression was significantly down-regulated in gastric carcinoma tissue specimens (P<0.001) compared with its expression in paired normal tissues. Furthermore, a Kaplan–Meier analysis revealed that lower levels of circLMTK2 expression were associated with decreased overall survival (OS) (P<0.001), and a multivariate Cox hazards analysis showed that high circLMTK2 expression was an independent factor for OS. Afterward, overexpression of circLMTK2 was performed in gastric cancer cell line MGC-803, and results indicated that malignant biological properties were inhibited by circLTMK2 overexpression. The present study showed the first evidence that circLMTK2 was down-regulated in GC, suggesting it as a novel biomarker for prognosis, and also as a therapeutic target in treatment of GC.
Highlights
Most human pre-mRNAs exist in linear forms that retain the exon order
A comparative analysis of circLMTK2 and LMTK2 mRNA expression was performed in BGC-823 cells that had been treated with the transcription inhibitor, actinomycin D
The above results suggested that circLMTK2 was a stable circular RNA expressed in Gastric cancer (GC) cells
Summary
Most human pre-mRNAs exist in linear forms that retain the exon order. Recently, high-throughput RNA sequencing and computational analyses have revealed that circular transcripts from genetic loci were widespread in the eukaryotic transcriptome [1,2], and a series of circular RNAs (circRNAs) were found to be abundantly and stably expressed in various tissues and across different species [3,4,5,6]. CircRNAs are characterized by their covalently closed loop structures generated from back-spliced exons, and have been identified as a novel class of diverse endogenous non-coding RNAs that might regulate gene expression in eukaryotic cells [7,8]. An increasing number of studies suggest that circRNAs are involved in the development and progression of various cancer types, and they may become potential molecular biomarkers and targets for cancer treatment. Gastric cancer (GC) remains one of the most common cancer types in the world, and has a high incidence in East Asia [9]. It is critically important to identify novel biomarkers and prognostic indicators that reflect disease status, and develop appropriate therapeutic plans for GC patients. The circRNA hsa circ 0001725, termed circLMTK2, is generated by the LMTK2 gene, and was screened
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