Long Noncoding RNA PSMA3 Antisense RNA 1 Promotes Cell Proliferation, Migration, and Invasion in Pancreatic Ductal Adenocarcinoma Via Targeting MicroRNA-154-5p to Positively Modulate Karyopherin Subunit Alpha 4

Abstract

Pancreatic ductal adenocarcinoma (PDAC), as the most frequent pancreatic tumor, featuring high death rate. The current study intends to explore the biological role of PSMA3 antisense RNA 1 (PSMA3-AS1) and its mechanism underlying PDAC progression. Expression analyses were conducted using quantitative reverse transcription-polymerase chain reaction. Proliferative, apoptotic, migratory, and invasive capacities were determined by functional assays, encompassing 5-ethynyl-2'-deoxyuridine, colony formation, JC-1, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and transwell assays in PDAC cells. The RNA-binding protein immunoprecipitation, RNA pulldown, and luciferase reporter assays uncovered the biological and regulatory role of PSMA3-AS1 in PDAC. Long noncoding RNA PSMA3-AS1 was aberrantly overexpressed in PDAC cells. Downregulated PSMA3-AS1 repressed cell proliferative, migratory, and invasive capacities and propelled cell apoptosis of PDAC. MicroRNA-154-5p (miR-154-5p) was proved to be targeted by PSMA3-AS1 in PDAC cells. Karyopherin subunit alpha 4 (KPNA4) was the downstream target messenger RNA of miR-154-5p. Karyopherin subunit alpha 4 knockdown hindered cell proliferation, migration, and invasion in PDAC. In rescue assays, KPNA4 overexpression or miR-154-5p interference counteracted the inhibitory influence of PSMA3-AS1 ablation on the progression of PDAC cells. Our results suggested that PSMA3-AS1 enhances PDAC cell proliferative, migratory, and invasive capacities via modulating miR-154-5p/KPNA4 axis.