CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis

Author:

Liu Yun,Cao Jia,Yang Qi,Zhu Linqi,Zhao Wenjun,Wang Xiuping,Yao Jun,Zhou Yong,Shao Shihe

Abstract

Abstract Background Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. Methods The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. Results CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. Conclusions Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

Funder

Jiangsu Funding Program for Excellent Postdoctoral Talent

the Top-level Clinical Discipline Project of Shanghai Pudong

Zhenjiang Key research and Development Plan Social development project

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Applied Mathematics,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics,Immunology

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