Abstract

BackgroundCircular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression.MethodsCircNet was used to screen potential circRNAs and validated circYAP1 expression levels in 17 GC tissues by quantitative real-time PCR (qRT-PCR) and another 80 paired GC tissues by FISH. CircYAP1 overexpression and knockdown experiments were conducted to assess the effects of circYAP1 in vitro and in vivo, and its molecular mechanism was demonstrated by RNA in vivo precipitation assays, western blotting, luciferase assay and rescue experiments.ResultsCircYAP1 expression level was significantly lower in GC tissues than the adjacent normal tissues, and GC patients with circYAP1 low expression had shorter survival times as compared with those with circYAP1 high expression. Functionally, circYAP1 overexpression inhibited cell growth and invasion in vitro and in vivo, but its knockdown reversed these effects. Further analysis showed that circYAP1 sponged miR-367-5p to inhibit p27 Kip1 expression and GC progression.ConclusionOur findings demonstrate that circYAP1 functions as a tumor suppressor in GC cells by targeting the miR-367-5p/p27 Kip1 axis and may provide a prognostic indicator of survival in GC patients.

Highlights

  • Circular RNAs are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear

  • We found that circYAP1 expression was lower in GC patients with a tumor size (TS) ≥ 5 cm than those with a TS < 5 cm (Additional file 2: Figure S1a)

  • Compared with that in GC tissue, the circYAP1 expression level in adjacent normal tissue was higher in 59 GC patients and lower in 21 GC patients (Fig. 1c, P < 0.0001)

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Summary

Introduction

Circular RNAs (circRNAs) are a new type of non-coding RNAs and their functions in gastric cancer (GC) remain unclear. Recent studies have revealed that circRNAs play an important role in cancer development and certain types of pathological responses, acting as microRNA (miRNA) sponges to regulate gene expression. Recent studies have shown that circular RNAs (circRNAs) are aberrantly expressed in GC, lung cancer, hepatocellular carcinoma (HCC) and colorectal cancer (CRC), involved in cancer development [5]. CircRNAs are a special type of ncRNAs derived from exons, introns or intergenic regions that are covalently linked to form a closed circular structure without 5′ caps and 3′ tails, display cell or tissue-specific expression, and are conserved across species due to their resistance to RNase R [6,7,8]. Compared with linear RNAs, circRNAs are remarkably stable, and accumulate

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