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.

Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3

“… 24 Chen et al found that DARS-AS1 could promote the proliferation of cervical cancer cells via miR-628-5p/JAG1 axis. 25 However, the mechanisms by which DARS-AS1 regulates the proliferation, apoptosis and invasion in cervical cancer cells remain largely unclear. In the present study, we found that downregulation of DARS-AS1 significantly inhibited the proliferation of cervical cancer cells via inducing apoptosis.…”

miR-23b-3p, miR-124-3p and miR-218-5p Synergistic or Additive Effects on Cellular Processes That Modulate Cervical Cancer Progression? A Molecular Balance That Needs Attention

“…Through their interaction with various cellular proteins, E6 and E7 activate Fas, MAPK, Akt, PI3K, and Wnt signaling pathways, which modulate cellular proliferation, migration, invasion, and apoptosis, as well as epithelial–mesenchymal transition (EMT) and metastasis [ 6 , 7 , 8 , 9 , 10 , 11 ], cellular processes that modulate CC progression [ 12 , 13 , 14 ]. The dysregulation in the function of proteins, signaling pathways, and cellular processes, result from altered gene expression [ 15 , 16 ]. Viral oncoproteins, the accumulation of genetic and epigenetic alterations, and post-translational modifications lead to the inactivation of tumor suppressor genes, activation of oncogenes, and increase or decrease the expression of microRNAs (miRNAs) [ 17 , 18 ].…”

WFDC21P promotes triple-negative breast cancer proliferation and migration through WFDC21P/miR-628/SMAD3 axis

“…The dysregulation of miRNAs is involved in multiple biological processes, including the proliferation, migration, differentiation, and apoptosis of cancer cells ( 37 ). miR-628-5p functions as a tumor-suppressive gene in pancreatic ductal adenocarcinoma by regulating AKT, in gastric cancer by targeting PIN1, and in cervical cancer by regulating JAG1 ( 38 – 40 ). However, the roles of miR-628-5p in TNBC remain unclear.…”