CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA throug
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RESEARCH
Open Access
CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p Dawei Rong1†, Chen Lu1†, Betty Zhang2, Kai Fu1, Shuli Zhao3*, Weiwei Tang1* and Hongyong Cao1*
Abstract Background: Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure, but its functions remain largely unknown. Growing evidence has revealed that circRNAs play a striking role as functional RNAs in the progression of malignant disease. However, the precise role of circRNAs in gastric cancer (GC) remains unclear. Methods: CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase reaction. Luciferase reporter, RNA pull down, and fluorescence in situ hybridization assays were employed to test the interaction between circPSMC3 and miR-296-5p. Ectopic over-expression and siRNA-mediated knockdown of circPSMC3, proliferation, migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPSMC3. Results: CircPSMC3 rather than liner PSMC3 mRNA was down-regulated in GC tissues, corresponding plasmas from GC patients as well as GC cell lines compared to normal controls. Lower circPSMC3 expression in GC patients was correlated with higher TNM stage and shorter overall survival. Over-expression of circPSMC3 and miR-296-5p inhibitor could inhibit the tumorigenesis of gastric cancer cells in vivo and vitro whereas co-transfection of circPSMC3 and miRNA-296-5p could counteract this effect. Importantly, we demonstrated that circPSMC3 could act as a sponge of miR-296-5p to regulate the expression of Phosphatase and Tensin Homolog (PTEN), and further suppress the tumorigenesis of gastric cancer cells. Conclusion: Our study reveals that circPSMC3 can serve as a novel potential circulating biomarker for detection of GC. CircPSMC3 participates in progression of gastric cancer by sponging miRNA-296-5p with PTEN, providing a new insight into the treatment of gastric cancer. Keywords: Gastric cancer, circPSMC3, miR-296-5p, PTEN, Therapy
Introduction Gastric cancer (GC) is the fifth most common cancer in the world and the third most common cause of cancer death worldwide [1]. It tends to metastasize into neighboring tissues and organs through lymph nodes and * Correspondence: [email protected]; [email protected]; [email protected] † Dawei Rong and Chen Lu contributed equally to this work. 3 Department of General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China 1 Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China Full list of author information is available at the end of the article
generate more cancer cells through the blood [2]. Although there have been many advancements in the diagnosis and treatment of GC, recurrence and metastasis are still occurring at high rates [3, 4]. Improvements in clinical care for these patients are limited b
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