CircRNA has_circ_0001946 promotes cell growth in lung adenocarcinoma by regulating miR-135a-5p/SIRT1 axis and activating Wnt/β-catenin signaling pathway

Abstract

Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of human cancers. However, little is known about the biological role and mechanism of circRNAs in lung adenocarcinoma (LAC). In the present study, we applied microarray analysis to screen for LAC-specific circRNAs. Top ten upregulated circRNAs were chosen for qRT-PCR analysis. Among them, circ_0001946 was significantly overexpressed in both LAC tissues and cell lines. In addition, the expression level of circ_0001946 was positively correlated with TNM stage and tumor size. Using Kaplan-Meier analysis, we found that circ_0001946 expression was negatively related with the overall survival of LAC patients. Next, we treated LAC cells with circ_0001946-specific shRNAs and found that knockdown of circ_0001946 inhibited LAC cell growth in vitro and in vivo. Mechanism investigation revealed that circ_0001946 was located in the cytoplasm of LAC cells and acted as a molecular sponge of miR-135a-5p to upregulate Sirtuin 1 (SIRT1) expression. Rescue assays further validated the role of circ_0001946-miR-135a-5p-SIRT1 axis in LAC progression. Additionally, SIRT1 has been demonstrated to be a positive regulator of Wnt/β-catenin signaling pathway. Western blot analysis revealed that circ_0001946 regulated SIRT1/Wnt/β-catenin signaling pathway. In conclusion, our findings suggested that circ_0001946 might be a potential biomarker for the diagnosis or treatment of LAC.