RESUMEN
BACKGROUND: Long noncoding RNA (LncRNA) XIST is one of the genes that exists in different types of cancers. Earlier researches showed that XIST can advance the progression of colorectal cancer. Nevertheless, the potential molecular mechanism of XIST in combination with miR-93-5p has not been explored in colorectal cancer. METHODS: We performed qRT-PCR to explore the level of XIST. And a serious experiments in vitro and in vivo were performed to explore the function of XIST. The relationship between XIST/HIF-1A and miR-93-5p was confirmed by RIP and dual-luciferase assays. RESULTS: In the present research, our team demonstrated the upregulation of XIST expression, which was related to tumor progression, and the downregulation of miR-93-5p in cells and tissues of colorectal cancer. XIST is the competitive endogenous RNA of miR-93-5p to promote HIF-1A, and then the upregulated AXL level facilitates the EMT process, migration, and proliferation of colorectal cancer. At last, we proved that XIST enhanced the in vivo and in vitro activities of colorectal cancer by regulating AXL signaling. CONCLUSION: In summary, the above results indicate that XIST promotes colorectal cancer tumorigenesis by regulating miR-93-5p/HIF-1A/AXL signaling pathway, which will supply a novel perspective to diagnose and treat colorectal cancer disease.
Asunto(s)
Neoplasias Colorrectales/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , MicroARNs/genética , Proteínas Proto-Oncogénicas/metabolismo , ARN Largo no Codificante/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Anciano , Animales , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , ARN Largo no Codificante/metabolismo , Proteínas Tirosina Quinasas Receptoras/genética , Transducción de Señal , Regulación hacia Arriba , Tirosina Quinasa del Receptor AxlRESUMEN
LncRNAs play pivotal roles in many important biological processes, but research on the functions of lncRNAs in human disease is still in its infancy. Therefore, it is urgent to prioritize lncRNAs that are potentially associated with diseases. In this work, we developed a novel algorithm, LncPriCNet, that uses a multi-level composite network to prioritize candidate lncRNAs associated with diseases. By integrating genes, lncRNAs, phenotypes and their associations, LncPriCNet achieves an overall performance superior to that of previous methods, with high AUC values of up to 0.93. Notably, LncPriCNet still performs well when information on known disease lncRNAs is lacking. When applied to breast cancer, LncPriCNet identified known breast cancer-related lncRNAs, revealed novel lncRNA candidates and inferred their functions via pathway analysis. We further constructed the human disease-lncRNA landscape, revealed the modularity of the disease-lncRNA network and identified several lncRNA hotspots. In summary, LncPriCNet is a useful tool for prioritizing disease-related lncRNAs and may facilitate understanding of the molecular mechanisms of human disease at the lncRNA level.