Hsa_circ_0069244 acts as the sponge of miR-346 to inhibit non-small cell lung cancer progression by regulating XPC expression

Abstract

Circular RNAs (circRNAs) play a significant role in the progression of diverse malignancies. Here, we aimed to probe the function and mechanism of circ_0069244 in non-small cell lung cancer (NSCLC). In the present study, circ_0069244 was selected from the circRNA microarray datasets (GSE112214). Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to examine circ_0069244, miR-346 and XPC complex subunit, DNA damage recognition and repair factor (XPC) expression levels. Kaplan-Meier curve was employed to analyze the association between circ_0069244 expression and overall survival of NSCLC patients. Cell counting kit-8 (CCK-8) and 5-Bromo-2'-deoxyuridine (BrdU) experiments were utilized to examine the proliferation of NSCLC cells. Scratch healing and Transwell experiments were executed to examine the migration of NSCLC cells. Western blot was conducted to detect XPC expression at protein level in NSCLC cells. Bioinformatics analysis, dual-luciferase reporter gene and RNA immunoprecipitation (RIP) experiments predicted and validated the targeting relationships of circ_0069244 and miR-346, as well as miR-346 and 3'untranslated region (UTR) of XPC mRNA, respectively. We reported that circ_0069244 was remarkably down modulated in NSCLC and was linked to shorter survival and poor tumor histological grade in NSCLC patients. Functionally, circ_0069244 repressed NSCLC cell proliferation and migration. Furthermore, miR-346-5p was unveiled to be a downstream target of circ_0069244, and miR-346-5p specifically modulated XPC expression. Rescue experiments indicated that the inhibitory effect of circ_0069244 was abolished by co-expression of miR-346-5p mimics. Taken together, circ_0069244 restrained NSCLC progression by modulating the miR-346-5p/XPC axis.