RESUMEN
Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.
Asunto(s)
Neoplasias Óseas , MicroARNs , Osteosarcoma , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proliferación Celular/fisiología , Movimiento Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
AIM: Hepatocellular carcinoma (HCC) is common and causes many deaths worldwide. The aim of this study is to explore the mechanism by which long non-coding RNA FGD5-AS1 regulates HCC cell proliferation and stemness. METHODS: Tumor and normal adjacent tissues were harvested from HCC patients. Real-time quantitative reverse transcription-PCR was applied to examine the expression of FGD5-AS1, miR-223, Epithelial cell transforming sequence 2 (ECT2) and FAT1. The protein levels of ECT2, FAT1, proliferating cell nuclear antigen (PCNA), OCT4, CD133 and CD90 were analyzed by western blot. The localization of FGD5-AS1 was examined by Fluorescence in situ hybridization. Cell proliferation was analyzed with CCK-8 and colony formation assays. Spheroid formation was used for analyzing cell stemness. Gene interaction was examined by RNA immunoprecipitation and luciferase activity assays. A subcutaneous xenograft mouse model was established to analyze HCC growth and stemness in vivo. Immunohistochemistry staining was used to analyze the expression PCNA and OCT4 in subcutaneous tumors. RESULTS: FGD5-AS1 was upregulated in HCC and its high expression indicated poor prognosis of patients. High expression of FGD5-AS1 enhanced HCC cell proliferation and stemness. Knockdown of FGD5-AS1 restrained tumor growth and stemness in mice. FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC. Both knockdown of miR-223 and overexpression of ECT2 and FAT1 reversed FGD5-AS1 silencing-mediated suppression of HCC cell proliferation and stemness. CONCLUSION: FGD5-AS1 directly sponged miR-223 and promoted the expression of ECT2 and FAT1 in HCC, thus enhancing HCC cell proliferation and stemness. Our study identifies potential prognostic biomarkers and therapeutic targets for HCC.