J-B Tian1, L Cao, G-L Dong. 1. Department of General Surgery, the Frist Medical Centre of Chinese of General Hospital, Haidian, Beijing, China. tianjingbo1226@126.com.
Abstract
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.
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.