RESUMEN
BACKGROUND: Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis. METHODS: Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo. RESULTS: PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells. CONCLUSIONS: We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.
Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , MicroARNs , ARN Largo no Codificante , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , ARN Largo no Codificante/genética , MicroARNs/genética , Proliferación Celular/genética , Ratones , Animales , Pronóstico , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Masculino , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Ratones Desnudos , Femenino , Línea Celular Tumoral , Metástasis de la Neoplasia , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cervical cancer is one of the most prevalent gynecological malignancies. Although the functions of long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and c-Myc in tumorigenesis have been acknowledged, the roles of c-Myc and lncRNA-PVT1 in the proliferation of cervical cancer are still unclear. Our study is designed to demonstrate the regulatory network involving c-Myc and lncRNA-PVT1 in cervical cancer. Quantitative real-time PCR and western blot assays were performed in our research to estimate the expression levels of RNA and proteins. CCK8 assays were applied to demonstrate the viability of HeLa and SiHa cells. Immunofluorescence assay was then used to investigate the co-localization of lncRNA-PVT1 and miR-486-3p. Binding of c-Myc to the promoter region of PVT1 was identified by ChIP-assay. Functionally, upregulation of lncRNA-PVT1 enhanced the proliferation and viability of cervical cancer cells. Mechanistically, lncRNA-PVT1 sponged miR-486-3p and released its repression of extracellular matrix protein 1. Besides, c-Myc functioned as an activator of lncRNA-PVT1 and upregulated its expression by binding to the promoter of PVT1 in cervical cancer cells. lncRNA-PVT1 was upregulated by c-Myc and thus enhanced the proliferation of cervical cancer cells by sponging miR-486-3p.
