Work

Circular RNA CDR1as Promotes Gastric Cancer Growth via miR-299-3p/TGIF1 Axis

Year: 2021

Type: preprint

Abstract: Background Gastric cancer (GC) is a common malignancy worldwide. Circular RNA CDR1as has been reported as a crucial regulator in human diseases including cancer. However, its biological roles, mechanisms and clinical values in GC remain largely unknown. Methods and Results CDR1as levels were surveyed in paired GC and adjacent normal tissues, paired blood samples from GC patients and healthy controls by RT-qPCR. Its clinical values were evaluated by ROC analysis, survival analysis and correlations with clinic pathological features. Cell transfection was performed to manipulate gene expression. In vitro CCK8 and colony formation assays and in vivo xenograft mouse model were employed to determine CDR1as effects on GC growth. CDR1as-miRNA and miRNA-mRNA interactions were predicted by bioinformatics analysis and further verified by RIP, dual-luciferase reporter gene assays, RT-qPCR, western blot and functional rescue experiments. Our results showed that CDR1as level was significantly downregulated in GC tissues and correlated with nerve invasion and poor prognosis. GC patients presented higher plasma CDR1as level than healthy controls. Functionally, knockdown of CDR1as inhibited GC cell proliferation and viability while its overexpression promoted GC growth in vitro and in vivo. The proliferation-related proteins PCNA and Cyclin D1 and apoptosis-related proteins Bax, Bcl-2, Caspase-3 and Caspase-9 were regulated. Mechanistically, CDR1as acted as a miR-299-3p sponge to relieve its suppressive effects and upregulate TGIF1 expression to promote GC growth.Conclusions CDR1as may be considered as a potential diagnostic and prognostic biomarker for GC. CDR1as/miR-299-3p/TGIF1 axis promotes GC growth in vitro and in vivo.

Source: Research Square

DOI: 10.21203/rs.3.rs-1081040/v1