RESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. METHODS: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. RESULTS: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. CONCLUSIONS: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.
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Proteínas de Unión al Calcio/genética , Carcinoma Hepatocelular/irrigación sanguínea , Factor de Transcripción E2F7/metabolismo , Neoplasias Hepáticas/irrigación sanguínea , MicroARNs/metabolismo , Quinasa de Cadena Ligera de Miosina/genética , ARN Largo no Codificante/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Pronóstico , ARN sin Sentido/genética , ARN sin Sentido/metabolismo , Transducción de Señal , TransfecciónRESUMEN
[This corrects the article DOI: 10.18632/oncotarget.17040.].
RESUMEN
BACKGROUND: Pancreatic cancer (PC) represents one of the most aggressive forms of cancer. The role of long non-coding RNAs (lncRNAs) has been highlighted in various malignancies including PC. The aim of the present study was to investigate the effects associated with actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on the progression of PC and the underlying mechanism. METHODS: Microarray-based gene expression profiling of PC was performed to identify PC-related lncRNAs, after which the expression of AFAP1-AS1 and cancer stem cell (CSC) markers in PC tissues and cells were determined accordingly. The potential microRNA-384 (miR-384) capable of binding to AFAP1-AS1, in addition to its ability to regulate activin receptor A type I (ACVR1) were analyzed. In order to investigate the effect of the AFAP1-AS1/miR-384/ACVR1 axis on self-renewal ability, tumorigenicity, invasion, migration and stemness of PC cells, shRNA-AFAP1-AS1, miR-384 mimic and inhibitor were cloned into cells. RESULTS: High expression of AFAP1-AS1 and ACVR1 with low expression of miR-384 were detected in PC tissues. ACVR1 was determined to be down-regulated when miR-384 was overexpressed, while the inhibition of AFAP1-AS1 decreased its ability to binding competitively to miR-384, resulting in the down-regulation of ACVR1 and enhancing miR-384 expression, ultimately inhibiting the progression of PC. The knockdown of AFAP1-AS1 or overexpression of miR-384 was confirmed to impair PC cell self-renewal ability, tumorigenicity, invasion, migration and stemness. CONCLUSIONS: Taken together, AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on PC cell stemness and tumorigenicity.
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Receptores de Activinas Tipo I/metabolismo , MicroARNs/metabolismo , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Animales , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Xenoinjertos , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptor Cross-Talk/fisiologíaRESUMEN
Accumulating evidence suggested that long non-coding RNAs (lncRNAs) play essential roles in various biological processes, including tumorigenesis. Aberrant expression of LINC00161 has been reported in some cancer types, however, the association of LINC00161 and hepatocellular carcinoma (HCC) has not been evaluated. Here, we measured the expression of LINC00161 in HCC tissues and corresponding normal liver tissues using real-time PCR. The result showed that the expression level of LINC00161 was significantly higher in HCC tissues. Further analysis indicated that HCC patients with higher LINC00161 expression have shorter survival. Multivariate Cox regression analysis showed that LINC00161 expression was an independent prognostic factor for the overall survival. Furthermore, our result indicated that knock-down of LINC00161 can significantly inhibit liver cancer cell migration and invasion. The present work indicated that LINC00161 might serve as an oncogenic gene and play a pivotal role in promoting tumor migration and invasion in HCC. Our work implicates the promising effect of LINC00161 on the prognosis of HCC.