USF1-induced overexpression of long noncoding RNA WDFY3-AS2 promotes lung adenocarcinoma progression via targeting miR-491-5p/ZNF703 axis.

Abstract

Lung adenocarcinoma (LUAD) is one of the most common diagnosed pathological categories of lung cancer. Long noncoding RNAs (lncRNAs) have been manifested to be key regulators in modulating multiple cancers. Nevertheless, the pathologic role of lncRNA WDFY3-AS2 in LUAD remains elusive. The relative messenger RNA and protein levels were assessed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses, respectively. Colony formation, carboxyfluorescein succinimidyl ester, terminal deoxynucleotidyl transferase dUTP nick-end labeling, wound-healing, and transwell invasion assays were performed to study the underlying role of WDFY3-AS2 in LUAD. Luciferase reporter assay, chromatin immunoprecipitation, RNA pull down, and RNA immunoprecipitation assays were conducted to probe into the interactions between relevant genes. WDFY3-AS2 expression was elevated in LUAD and WDFY3-AS2 transcription was activated by transcription factor USF1. Silencing WDFY3-AS2 could suppress cell proliferation, migration, and invasion, whereas accelerate cell apoptosis in LUAD. Molecular mechanism assays revealed that WDFY3-AS2 could bind to miR-491-5p and miR-491-5p inhibition could reverse the inhibitory effect of WDFY3-AS2 silence on LUAD progression. Besides, zinc finger protein 703 (ZNF703) was identified as a downstream target of miR-491-5p and its expression could be upregulated by WDFY3-AS2. Further, rescue assays uncovered that ZNF703 overexpression could restore the suppressive influence of silenced WDFY3-AS2 on LUAD development. USF1-acitvated WDFY3-AS2 promotes LUAD progression via targeting miR-491-5p/ZNF703 axis, suggesting the potential value of WDFY3-AS2 as a novel target for LUAD treatment.