RESUMO
OBJECTIVE: Increasing studies have confirmed long non-coding RNAs (lncRNAs) as novel regulators in tumorigenesis. LncRNA DDX11 antisense RNA 1 (DDX11-AS1) has been found to be abnormally expressed in several tumors. In this work, we aimed to evaluate its expressions and functions in colorectal cancer (CRC). PATIENTS AND METHODS: The Cancer Genome Atlas (TCGA) datasets were used for the identification of dysregulated lncRNA in CRC. The levels of DDX11-AS1 were determined in tumor tissues and cell lines by Real Time-Polymerase Chain Reaction (RT-PCR). The clinical significance of DDX11-AS1 in CRC patients was analyzed using Chi-square test and Kaplan-Meier analysis. Functional assays for the exploration of DDX11-AS1 and miR-873 were performed using a series of cells experiment. ChIP assay and luciferase reporter assays were used to explore the mechanism of actions of DDX11-AS1 in CRC cells. RESULTS: We identified DDX11-AS1 as a new CRC-related lncRNA whose levels were distinctly up-regulated in CRC specimens and cell lines, partly induced by YY1. Clinical explorations suggested that increased expressions of DDX11-AS1 in CRC were positively associated with lymph nodes metastasis and TNM stage and had a distinct influence on the overall survival. Further multivariate assays indicated that DDX11-AS1 was an independent prognostic parameter implying a poorer clinical outcome for patients with CRC. Functional assays revealed that the knockdown of DDX11-AS1 suppressed the proliferation, migration, and invasion of CRC cells, and stimulate apoptosis. Mechanistic studies showed that the up-regulation of DDX11-AS1 competitively bound to miR-873 prevented CLDN7 from miRNAs-mediated degradations, thus facilitated the CRC progress. Further rescue assays were carried out to achieve confirmation. CONCLUSIONS: Our present findings may enhance our understanding of the pathogenesis of CRC and revealed DDX11-AS11 as a potential therapeutic target for CRC.
Assuntos
Claudinas/metabolismo , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Transcrição YY1/metabolismo , Apoptose , Movimento Celular , Proliferação de Células , Distribuição de Qui-Quadrado , Claudinas/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Análise Multivariada , RNA Longo não Codificante/genética , Células Tumorais Cultivadas , Fator de Transcrição YY1/genéticaRESUMO
According to the physical and chemical properties of effective constituents in Tongxiening granules, experiments were conducted on physical, chemical and TLC identifications of this preparation. Reliable data may provide a basis for the establishment of its quality standards.