Abstract

Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers of various cancers. However, the effects of a novel circRNA termed circGRAMD1B in human gastric cancer (GC) remain unclear. A microarray was used to screen circRNA expression in GC. Quantitative real-time PCR was used to detect the expression of circGRAMD1B. Gain- and loss- of-function experiments were performed to investigate the biological functions of circGRAMD1B in vitro and vivo. Bioinformatics analysis, fluorescence in situ hybridization, dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and rescue experiments were conducted to confirm the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We screened differentially expressed circRNAs and found that circGRAMD1B expression was downregulated in GC tissues and cell lines. Functionally, circGRAMD1B acted as an anti-oncogene and inhibited the proliferation, migration, and invasion abilities of GC cells. Then, we verified that circGRAMD1B served as a sponge that targeted miR-130a-3p in GC cells; circGRAMD1B alleviated GC cell proliferation, migration, and invasion by targeting miR-130a-3p. A mechanistic analysis showed that PTEN and p21 were involved in circGRAMD1B/miR-130a-3p axis-inhibited GC tumorigenesis. Our findings suggest that circGRAMD1B plays an important role in GC progression by regulating miR-130a-3p-PTEN/p21, which may provide a potential biomarker and therapeutic target for GC.

Highlights

  • Gastric cancer (GC) is one of the most common malignant tumors and the third most frequent cause of cancer-related death worldwide [1]

  • The circular RNA PRMT5 promotes the metastasis of bladder carcinoma by sponging miR-30c and induces epithelialmesenchymal transition [18]

  • We demonstrated that circGRAMD1B was significantly decreased in gastric cancer (GC) tissues and cell lines and that lower circGRAMD1B expression in GC tissues was correlated with tumor size and T stage

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Summary

Introduction

Gastric cancer (GC) is one of the most common malignant tumors and the third most frequent cause of cancer-related death worldwide [1]. The complexity and pathogenic mechanism of GC are believed to be major obstacles; detailed research into the molecular mechanisms of GC is essential for improving the diagnosis and treatment [2]. Studies have confirmed that circRNAs participate in various biological and pathological processes, such as proliferation, migration, and invasion [8, 9]. These reports suggest that circRNAs gradually provide a potential perspective on cancer diagnosis and treatment. The specific function and molecular mechanism of most circRNAs in human GC remain mostly unknown. We aimed to identify circRNAs that may be involved in the pathology of GC using circRNA microarrays (Capitalbio, China). We screened and determined the expression and functions of circGRAMD1B

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