DARS-AS1 accelerates the proliferation of cervical cancer cells via miR-628-5p/JAG1 axis to activate Notch pathway.

ABSTRACT

BACKGROUND: Growing evidence has indicated the vital parts of long non-coding RNAs (lncRNAs) in modulating the progression of assorted human cancers, including cervical cancer (CC). Nevertheless, the role and mechanism of aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) have been not comprehensively illustrated in CC yet. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was exploited for assessing RNA expression while western blot for protein expression in CC cells. The cell counting kit-8 (CCK-8), colony formation and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays, as well as flow cytometry analysis, were employed to evaluate the modulation of DARS-AS1 on the proliferation and apoptosis of CC cells. In addition, RNA immunoprecipitation (RIP), RNA pull down assay and luciferase reporter assay confirmed the interactivity among DARS-AS1, miR-628-5p and jagged canonical Notch ligand 1 (JAG1). RBP-JK luciferase reporter assay determined the activity of Notch pathway. RESULTS: DARS-AS1 level was significantly increased in CC cells. Moreover, down-regulation of DARS-AS1 hampered cell the proliferation and accelerated the apoptosis of CC cells. Importantly, DARS-AS1 was a competing endogenous RNA (ceRNA) to elevate JAG1 level through sequestering miR-628-5p, leading to activated Notch pathway to aggravate CC tumorigenesis. CONCLUSIONS: DARS-AS1/miR-628-5p/JAG1/Notch signaling accelerates CC progression, indicating DARS-AS1 as a novel therapeutic target for patients with CC.