Circular RNA circ_HN1 facilitates gastric cancer progression through modulation of the miR-302b-3p/ROCK2 axis.

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality in the world. Circular RNA hsa_circHN1_005 (circ_HN1), also termed as hsa_circ_0045602, is reported as an oncogene in GC. However, the molecular mechanism of circ_HN1 in GC development has not been fully explored. Here, we surveyed the regulatory mechanism of circ_HN1 in GC progression. The levels of circ_HN1, miR-302b-3p, and rho-associated coiled-coil containing protein kinase 2 (ROCK2) mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, colony formation, cell cycle progresion, migration, and invasion were determined by using cell counting, flow cytometry, colony formation, or transwell assays. Protein levels were detected with Western blotting. The relationship between circ_HN1 or ROCK2 and miR-302b-3p was verified via dual luciferase reporter or RNA immunoprecipitation (RIP) assays. The role of circ_HN1 in vivo was confirmed by xenograft assay. We observed that circ_HN1 and ROCK2 were upregulated while miR-302b-3p was downregulated in GC tissues and cells. Circ_HN1 silencing slowed tumor growth in vivo and impeded cell proliferation migration, invasion, and facilitated cell apoptosis in GC cells in vitro. Circ_HN1 sponged miR-302b-3p to regulate ROCK2 expression. MiR-302b-3p inhibitor reversed circ_HN1 silencing-mediated influence on the malignant behaviors of GC cells. Furthermore, ROCK2 overexpression restored miR-302b-3p mimic-mediated impacts on cell malignant behaviors in GC cells. In conclusion, circ_HN1 exerted an oncogenic role in GC through upregulating ROCK2 via sponging miR-302b-3p, offering evidence that circ_HN1 is a potential target for GC therapy.

Downregulation of circular RNA circ-HN1 suppressed the progression of gastric cancer through the miR-485-5p/GSK3A pathway.

Gastric cancer (GC) is a malignancy with high incidence and mortality globally. Circular RNAs (circRNAs) are reported to regulate cellular processes in human diseases, including GC. Herein, the functions of circ-HN1 and its molecular mechanisms were investigated. circ-HN1, miR-485-5p, and GSK3A levels in GC were measured using Real time-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was analyzed using cell counting kit-8 (CCK-8) and colony formation assays. Meanwhile, the migration and invasion abilities were analyzed using the transwell assay. The targeted relationship was confirmed using a luciferase reporter assay and an RNA pull-down assay. In both GC tissues and cells, circ-HN1 expression was upregulated, and its silencing suppressed cellular processes. Moreover, circ-HN1 served as a sponge of miR-485-5p, which was reduced in patients with GC and negatively regulated by circ-HN1 in GC cells. Inhibition of miR-485-4p abolished the biological functions induced by the silencing of circ-HN1. Additionally, miR-485-5p targeted GSK3A in GC, whose expression was elevated in tumor tissues and was negatively correlated with miR-485-5p in tumor cells. GSK3A rescued the inhibition of miR-485-5p in the cellular processes. In conclusion, silencing of the circ-HN1-miR-485-5p-GSK3A regulatory network inhibited GC cell proliferation, migration, and invasion, suggesting that circ-HN1 is a potential target for GC therapy.

A novel circular RNA circ_HN1/miR-628-5p/Ecto-5'-nucleotidase competing endogenous RNA network regulates gastric cancer development.

The competing endogenous RNA (ceRNA) activity of circular RNAs (circRNAs) has been implicated in the development of gastric cancer. Here, we sought to explore the ceRNA function of circRNA Jupiter microtubule associated homolog 1 (circ_HN1) in gastric tumorigenesis. Circ_HN1, microRNA (miR)-628-5p, and NT5E expression levels were quantified by qRT-PCR and western blot. Dual-luciferase reporter assays were used to assess the direct relationship between miR-628-5p and circ_HN1 or NT5E. Our data showed that circ_HN1 expression was enhanced in human gastric cancer. Depletion of circ_HN1 impeded cell proliferation, spheroid formation, invasion, and migration and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. NT5E was a downstream effector of circ_HN1 function. NT5E was targeted and inhibited by miR-628-5p through the perfect complementary site in NT5E 3'UTR, and circ_HN1 affected NT5E expression through miR-628-5p competition. Moreover, depletion of miR-628-5p reversed the effects of circ_HN1 silencing on regulating cell functional behaviors. Our findings identify a novel ceRNA network, the circ_HN1/miR-628-5p/NT5E axis, for the oncogenic activity of circ_HN1 in gastric cancer, highlighting circ_HN1 inhibition as a promising targeted treatment against gastric cancer.