RESUMEN
The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. In this study, the expression of LINC01123 was significantly upregulated in OS cell lines than in a human osteoblast cell line. Furthermore, in vitro and in vivo experiments confirmed that knockdown of LINC01123 suppressed cell progression. Mechanistically, LINC01123 acted as a competing endogenous RNA by sponging miR-516b-5p, thus, increasing Gli1 expression by directly targeting its 3'UTR. Taken together, LINC01123 enhances OS proliferation and metastasis via the miR-516b-5p/Gli1 axis. Therefore, LINC01123 may be a potential therapeutic target for OS treatment.
Asunto(s)
Neoplasias Óseas/patología , Proteínas Hedgehog/metabolismo , MicroARNs/metabolismo , Osteosarcoma/patología , ARN Largo no Codificante/metabolismo , Proteína con Dedos de Zinc GLI1/metabolismo , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , MicroARNs/genética , Metástasis de la Neoplasia , Osteosarcoma/genética , Osteosarcoma/metabolismo , ARN Largo no Codificante/genética , Transducción de Señal , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
Osteosarcoma (OS) is a familiar malignant bone tumor that occurs mainly in adolescents. Immature colon carcinoma transcript-1 (ICT1) is an important member of the large mitoribosomal subunit in mitochondrial ribosomes, which has been shown to be closely related to tumorigenesis. Its expression and function in OS, however, remained unclear. Here, we showed that ICT1 was significantly upregulated in OS and promoted the growth of OS cells. Mechanistically, ICT1 acted as an oncogene in OS and promoted proliferation and inhibited apoptosis of OS cells through the STAT3/BCL-2 axis. These results reveal a novel insight into the role of the ICT1/STAT3/BCL-2 axis in OS and therefore may represent a novel molecular target for novel treatments.
Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , Osteosarcoma , Proteínas Ribosómicas , Animales , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Xenoinjertos , Humanos , Ratones , Ratones Desnudos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: MiR-1297 is reported to function as a tumor suppressor of various cancers. However, the role of miR-1297 in the development of osteosarcoma (OS) has not been elaborated. The purpose of this study was to investigate the functional effects of miR-1297 on OS progression and the underlying mechanism. METHODS: The expression of protein and mRNA in OS cells was evaluated by Western blotting and quantitative real-time polymerase chain reaction. Cellular proliferation was investigated by cell counting kit-8, colony formation and apoptosis assays. Bioinformatics methods were used to predict target genes. The relationship between PFKFB2 and miR-1297 was demonstrated by dual-luciferase reporter assay. Metabolic changes in OS cells were monitored using an XF96 metabolic flux analyzer. RESULTS: We found that miR-1297 was downregulated in OS and that lower expression of miR-1297 promoted proliferation and contributed to the Warburg effect in OS cells. Furthermore, we showed that silencing PFKFB2 inhibited proliferation and reduced aerobic glycolysis while overexpression of PFKFB2 reduced the anti-tumor function of miR-1297 in OS cells. Mechanistically, miR-1297 acted as a tumor suppressor in OS and reduced the expression of PFKFB2 by directly targeting its 3'UTR. CONCLUSION: The miR-1297/PFKFB2 axis regulated OS proliferation by controlling the Warburg effect. Our results revealed a previously undiscovered function of miR-1297 in OS, which strongly linked metabolic alterations with cancer progression. Targeting miR-1297 may become a promising therapeutic approach for OS.