The role of miR-485-5p/NUDT1 axis in gastric cancer

摘要

Cancers can survive the oxidative conditions by upregulating nucleoside diphosphate linked moiety X-type motif 1 (NUDT1). However, the mechanisms underlying gastric carcinogenesis and the dys-regulation of NUDT1 in gastric cancer (GC) remain unknown. Our study aimed to explore the role of NUDT1 and its regulatory pathway by miR-485-5p in GC. Gastric cancer tissues and paired noncancerous tissue samples were collected, and the expression level of NUDT1 and miR-485-5p were detected. Two cohorts from The Cancer Genome Atlas (TCGA) database and another cohort from the Tianjin Medical University Cancer Institute and Hospital were further analyzed. Luciferase assays were performed, and the effects of the miR-485-5p/NUDT1 axis on GC cells and normal gastric cells were determined by subsequent experiments. We found that the expression of miR-485-5p was clearly repressed in GC tissues, while NUDT1 expression level was dramatically increased. The overexpression of NUDT1 correlated closely with an increase in invasive depth and a decrease in survival in GC patients. MiR-485-5p could directly bind to the 3′UTR of NUDT1 mRNA and induce its degradation, thus down-regulate its expression. The miR-485-5p/NUDT1 axis could lead to the changes of 8-oxo-dG in GC cells. And the increased expression of NUDT1 resulting from the downregulation of miR-485-5p could accelerate cell proliferation and metastasis in GC. However, the growth and migration of normal gastric cells did not depend on the protection of NUDT1, while the overexpression of NUDT1 could promote malignant transition in normal gastric cells. MiR-485-5p acts as a tumor suppressor by targeting NUDT1 in GC. The miR-485-5p/NUDT1 axis is involved in the processes of cell growth and cell motility and plays a key role in the tumorigenesis of GC.