Abstract
BackgroundAbnormally expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC).MethodsThe relative expression levels of lncRNA AFAP1-AS1, microRNA (miR)-107 and pyruvate dehydrogenase kinase isozyme 4 (PDK4) mRNA were assessed by quantitative real-time PCR. PDK4, PCNA and cyclin D1 expression levels were determined using Western blot analysis. Bioinformatics analysis and dual-luciferase gene reporter assay were conducted for identifying and validating the binding sequences between AFAP1-AS1 and miR-107, as well as between miR-107 and PDK4. Cell counting kit-8 assay was employed for detecting cell proliferation. Cell migration and invasion abilities were examined using Transwell assays.ResultsThe present study revealed that AFAP1-AS1 expression was elevated in OC cells and tissues. AFAP1-AS1 expression and FIGO stage were positively correlated. AFAP1-AS1 knockdown repressed OC cell proliferation, migration and invasion. AFAP1-AS1 functioned as a sponge of miR-107, and miR-107 reversed the effects of AFAP1-AS1 on OC cells. It was validated that miR-107 was able to bind to PDK4, and AFAP1-AS1 regulated PDK4 expression by competitively binding with miR-107. Additionally, miR-107 modulated OC cell proliferation, migration and invasion via targeting PDK4.ConclusionsLncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/PDK4 axis.
Highlights
Ovarian cancer (OC) is the second most common cause of cancer-related deaths among women [1]
LncRNA AFAP1-AS1 serves as a tumor driver in the pathogenesis of OC via the miR-107/pyruvate dehydrogenase kinase isozyme 4 (PDK4) axis
AFAP1-AS1 was highly expressed and was associated with poor prognosis in OC The Quantitative real-time PCR (qRT-PCR) was used to detect AFAP1-AS1 expression in OC cells and tissues, and it was shown that in comparison with normal human ovarian surface epithelial cell line (IOSE80) or adjacent tissues, AFAP1-AS1 expression was dramatically enhanced in OC tissues and cell lines (Fig. 1a&b)
Summary
Ovarian cancer (OC) is the second most common cause of cancer-related deaths among women [1]. Recognized as a class of functional RNA molecule whose transcripts are over 200 nt long, long non-coding RNAs (lncRNAs) modulate gene expression at the epigenetic, transcriptional and post-transcriptional levels, thereby participating widely in the physiological and pathological processes [4, 5]. AFAP1-AS1 facilitates the tumorigenesis and epithelial-mesenchymal transition of triplenegative breast cancer via the Wnt/β-Catenin signal pathway [10]. AFAP1-AS1 facilitates non-small cell lung cancer cell migration and invasion by up-regulating the IRF7 and RIG-I-like receptor signaling pathways [11]. Expressed in various tumors, long non-coding RNAs (lncRNAs) feature prominently in tumor development, yet little is still known regarding the functional roles of lncRNA AFAP1 antisense RNA 1 (AFAP1-AS1) in ovarian cancer (OC)
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