Activation of circ_0072088/miR-1261/PIK3CA pathway accelerates lung adenocarcinoma progression

Abstract

Background: Circular RNAs (circRNAs) are involved in the tumorigenesis and progression of lung adenocarcinoma (LUAD). This study aimed to determine the role of circ_0072088 in LUAD.

Methods: The existence and expression of circ_0072088 in human LUAD tissues and cell lines were determined through Sanger sequencing, quantitative reverse transcription-polymerase chain reaction, and fluorescence in situ hybridization (FISH). Subsequently, the biological role of circ_0072088 was examined using loss-of-function assays in H1299 cells. Moreover, circ_0072088/miR-1261/PIK3CA pathway-mediated biological effects in H1299 were verified using bioinformatic prediction and experiments, including interaction analysis (FISH, luciferase reporter, and RNA-pulldown assays), and tumor biological function test (CCK8 and colony formation, wound healing, and transwell assays). Finally, miR-1261 and PIK3CA expression and LUAD patient survival were further analyzed using FISH, immunohistochemical staining, and the Kaplan-Meier plotter database, respectively.

Results: First, an increase in circ_0072088 was confirmed in human LUAD tissues. Thereafter, it was mainly localized in the cytoplasm and was found to enhance cell proliferation, migration, and invasion of H1299 cells. Mechanistically, circ_0072088 directly downregulated miR-1261 expression, whereas increased PIK3CA gene expression was associated with poor overall survival of LUAD patients. The activation of the circ_0072088/miR-1261/PIK3CA regulatory pathway may play a significant role in the tumorigenesis and progression of LUAD.

Conclusions: Circ_0072088-dependent regulation of miR-1261/PIK3CA is important for cell proliferation, migration, and invasion during the tumorigenesis and progression of LUAD, warranting the need to consider the circ_0072088/miR-1261/PIK3CA regulatory pathway as a potential therapeutic target in patients with lung adenocarcinoma.

Keywords: bioinformatics; cell lines; circRNAs; lung adenocarcinoma; tumorigenesis.