Abstract
BackgroundGrowing 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.MethodsReal-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.ResultsDARS-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.ConclusionsDARS-AS1/miR-628-5p/JAG1/Notch signaling accelerates CC progression, indicating DARS-AS1 as a novel therapeutic target for patients with CC.
Highlights
Growing evidence has indicated the vital parts of long non-coding RNAs in modulating the progression of assorted human cancers, including cervical cancer (CC)
GEPIA data indicated an evident overexpression of DARS-AS1 in CESC samples compared to normal ones (Fig. 1a)
We detected the elevated expression of DARS-AS1 in CC cell lines (HeLa, C33A, MS751, SiHa, ME-180 and CaSki) relative to human normal cervical epithelial cell line (Ect1/E6E7) using Real-time quantitative polymerase chain reaction (RT-qPCR) method (Fig. 1b)
Summary
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). The role and mechanism of aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1) have been not comprehensively illustrated in CC yet. It is achievable to reduce CC incidence and the mortality rates of CC patients though. As a kind of non-coding RNAs, long non-coding RNAs (lncRNAs) exceeding 200 nucleotides present various modulatory roles like epigenetic, transcriptional, or post-transcriptional regulations [8]. As for aspartyl-tRNA synthetase antisense RNA 1 (DARS-AS1), it was previously found to actively involve into the progression of ovarian cancer [13], and to facilitate malignant development in thyroid cancer [14]. The function and regulatory way of DARS-AS1 in CC have not been illustrated yet
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