Long noncoding RNA ITGB2‐AS1 promotes growth and metastasis through miR‐4319/RAF1 axis in pancreatic ductal adenocarcinoma

Abstract

Long noncoding RNA (lncRNA) has been considered as potentially critical regulators in pancreatic ductal adenocarcinoma (PDAC). In this study, we prospectively investigate the effect and mechanism of lncRNA integrin subunit beta 2‐anti‐sense RNA 1 (ITGB2‐AS1) on regulation of PDAC progression. The expression of ITGB2‐AS1 and its target were analyzed by quantitative real‐time polymerase chain reaction and in situ hybridization. 3‐(4,5‐Dimethylthiazol‐z‐yl)‐2,5‐diphenyltetrazolium bromide, flow cytometry, wound healing, and transwell assays were used to investigate the influence of ITGB2‐AS1 on cell proliferation, cell cycle, migration, and invasion, respectively. The interaction between ITGB2‐AS1 and its target was determined via luciferase activity assay and RNA immunoprecipitation. The subcutaneous xenotransplanted tumor model was established and employed to detect the tumorigenic function of ITGB2‐AS1, which was evaluated by western blot analysis, immunohistochemistry, and hematoxylin and eosin staining. The results showed that ITGB2‐AS1 was elevated in both PDAC tumor tissues and cell lines, predicting a poor prognosis in PDAC patients. Knocking down of ITGB2‐AS1 suppressed PDAC cell proliferation, invasion, and migration but induced cell apoptosis in vitro. Moreover, ITGB2‐AS1 could target and inhibit the expression of miR‐4319 and miR‐4319‐targeted and ‐suppressed serine/threonine kinase RAF1. ITGB2‐AS1 promoted PDAC progression via inhibition of miR‐4319. Interference of ITGB2‐AS1 could suppress in vivo tumorigenic ability of PDAC via downregulation of RAF1. In conclusion, ITGB2‐AS1 promoted PDAC progression via sponging miR‐4319 to upregulate RAF1, suggesting the potential therapeutic target ability of ITGB2‐AS1 in PDAC.