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

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.

Downstream Target Analysis for miR-365 among Oral Squamous Cell Carcinomas Reveals Differential Associations with Chemoresistance

“…More detailed analysis of ubiquitin protein ligase, or UBR3, has revealed this may involved in regulated levels of the DNA repair protein APE1, which is considered ess tial for genomic repair and long-term stability [37]. Although one previous report ide fied UBR3 as involved with screening studies in breast cancers, this may be the first rep of differential expression in oral cancers [38]. Moreover, the fact that UBR3 is most hig expressed in the most rapidly growing and most chemoresistant cell lines (SCC25, SC may suggest that miR-365 modulation of this downstream target may be a significant m diator of oral cancer proliferation and progression [21][22][23][24].…”

Emerging roles of circular RNAs in tumorigenesis, progression, and treatment of gastric cancer

“…On the other hand, H. pylori can also downregulate certain circRNAs. The expression of circRNA_15430 was reduced in H. pylori -positive gastritis tissues and H. pylori -infected MGC-803 cells, which promoted the proliferation and migration of GC cells while suppressing apoptosis and autophagy through the miR-382-5p/zinc finger CCHC-type containing 14 pathways [ 118 ]. These results demonstrate that circRNAs can be developed as therapeutic targets.…”