RESUMEN
BACKGROUND: Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis. OBJECTIVE: In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC. METHODS: Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting. RESULTS: UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p. CONCLUSION: These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.
Asunto(s)
MicroARNs , Neoplasias Ováricas , ARN Largo no Codificante , Femenino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Ováricas/genética , ARN Mensajero , Proteínas Serina-Treonina QuinasasRESUMEN
The human genome transcribes a large amount of non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs. LncRNAs and microRNAs have been shown to play a critical regulatory role in tumorigenesis and progression. Competitive endogenous RNAs (ceRNAs) affect other RNAs transcription through competitively binding to common microRNAs (miRNAs). MALAT1 is a typical lncRNA that is markedly up-regulated in breast cancer. However, current understanding of the involvement of MALAT1 in breast cancer development and prognosis remains unclear. In the present study, the expression of MALAT1 in clinical samples of breast cancer tissues was found to be significantly up-regulated that was consistent with the result based on the dataset of the Cancer Genome Atlas (TCGA) at cBioportal. A negative correlation between overall survival and the expression of MALAT1 was statistically significant in the group of diagnosis age below 60 or in the group of infiltrating ductal carcinoma analyzed by TCGA database, which declared that MALAT1 might be a potentially useful prognostic factor. Furthermore, the combination of bioinformatics prediction with experimental verifications indicated that lncRNA MALAT1 can regulate BLCAP mRNA expression through binding to miR-339-5p.
