Regulatory network of circRNA\u2013miRNA\u2013mRNA contributes to the histological classification and disease progression in gastric cancer

Jia Cheng,Huiqin Zhuo,Jigui Peng,Jianchun Cai,Linpei Wang,Mao Xu,Hao Xu,Jingjing Hou,Lingyun Lin

doi:10.1186/s12967-018-1582-8

Abstract

BackgroundLittle has been known about the role of non-coding RNA regulatory network in the patterns of growth and invasiveness of gastric cancer (GC) development.MethodsMicroRNAs (miRNAs) microarray was used to screen differential miRNA expression profiles in Ming’s classification. The significant differential expressions of representative miRNAs and their interacting circular RNA (circRNA) were confirmed in GC cell line and 63 pairs of GC samples. Then, a circRNA/miRNA network was constructed by bioinformatics approaches to identify molecular pathways. Finally, we explored the clinical value of the common targets in the pathway by using receiver operating characteristic curve and survival analysis.ResultsSignificantly differential expressed miRNAs were found in two pathological types of GC. Both of miR-124 and miR-29b were consistently down-regulated in GC. CircHIPK3 could play a negative regulatory role on miR-124/miR-29b expression and associated with T stage and Ming’s classification in GC. The bioinformatics analyses showed that targets expression of circHIPK3-miR-124/miR-29b axes in cancer-related pathways was able to predict the status of GC and associated with individual survival time.ConclusionsThe targets of circHIPK3-miR-124/miR-29b axes involved in the progression of GC. CircHIPK3 could take part in the proliferation process of GC cell and may be potential biomarker in histological classification of GC.

Highlights

Little has been known about the role of non-coding RNA regulatory network in the patterns of growth and invasiveness of gastric cancer (GC) development
MiR‐124 and miR‐29b were negatively regulated by circHIPK3 in GC cell With quantitative reverse transcription polymerase chain reaction (qRT-PCR), we verified that the expression levels of miR-124 and miR-29b were both significantly decreased in human GC tissues compared with their paired normal gastric tissues (Fig. 2a, b, n = 63)
In 1977, Ming provided an original classification based on tumor biological characteristics of (See figure on page.) Fig. 5 Up-regulated mRNA expression levels of target genes mediated by circHIPK3-miR-124/miR-29b axes revealed by Oncomine analyses in 80 GC cases. a Over-expression of circHIPK3 increased the mRNA expression of collagen type IV alpha chain (COL4A1), collagen type I alpha 1 chain (COL1A1) and Cyclin-dependent kinases 6 (CDK6). b Knockdown of circHIPK3 inhibits mRNA expression of COL4A1, COL1A1 and CDK6. c–e Expressions of COL1A1, COL4A1 and CDK6 were found to be upregulated comparing with normal gastric tissues, respectively. f–h Receiver operating characteristic (ROC) curve revealed clinical value of COL1A1 and COL4A1 but not CDK6 in the screening of GC. *P < 0.05, **P < 0.01, ***P < 0.001

Summary

Introduction

Little has been known about the role of non-coding RNA regulatory network in the patterns of growth and invasiveness of gastric cancer (GC) development. Gastric cancer (GC) is an important public health problem in most parts of the world [1,2,3]. Environmental pathogenic factors and individual genetic background were thought to result in the gastric carcinogenesis. Genetic risk was found to affect around 10% of cases with GC in familial clustering study [2]. Mutations of some risk genes have been identified as genetic basis of GC. The exact molecular mechanism and the risk gene regulatory network of GC are far from the clear

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Discussion

Conclusion