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.
Subject(s)
Claudins/metabolism , Colorectal Neoplasms/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , YY1 Transcription Factor/metabolism , Apoptosis , Cell Movement , Cell Proliferation , Chi-Square Distribution , Claudins/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Female , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Lymph Nodes/metabolism , Lymph Nodes/pathology , Male , MicroRNAs/genetics , Middle Aged , Multivariate Analysis , RNA, Long Noncoding/genetics , Tumor Cells, Cultured , YY1 Transcription Factor/geneticsABSTRACT
Objective: To compare the efficacy and safety of colorectal resection combined with simultaneous radiofrequency ablation (RFA) in the treatment of synchronous colorectal liver metastases(SCRLM). Methods: This retrospective study involved the patients admitted between January 1st 2010 and September 1st 2013. A total of 20 patients who underwent colorectal resection combined with simultaneous RFA of SCRLM were enrolled. Those patients (RFA group) were matched with 20 patients (Resection group) who underwent simultaneous resections of colorectal cancer and SCRLM based on the propensity scores. Perioperative parameters and survival outcomes were compared between the two groups. Results: The RFA and Resection groups were comparable in demographics, cancer characteristics and chemotherapy treatment (all P>0.05). The estimated blood loss and intraoperative blood transfusions in the RFA group were significantly lower than those in the resection group [150.00(100.00-200.00) vs 200.00(112.50-650.00), 1 vs 7, all P>0.05]. The postoperative stay in the RFA group was significantly shorter than that in laparoscopic group [8.50(8.00-10.75) vs 11.00(8.25-14.25), P=0.043]. There was no significant difference in postoperative complications (P>0.05). The 3-year disease free survival rate was 14.00% in the RFA group, and 31.20% in the Resection group (P=0.047). However, the 3-year overall rates were similar between the two groups (P>0.05). Conclusions: Compared with simultaneous resections of colorectal cancer and SCRLM resections, colorectal resection combined with simultaneous RFA of SCRLM was associated with less surgical blood loss and shorter hospitalization. Although inferior to simultaneous resections of colorectal cancer and SCRLM resections in survival outcomes, this approach extends the capability of delivering potentially curative treatment for colorectal cancer patients with unresectable SCRLM.
Subject(s)
Catheter Ablation , Colorectal Neoplasms/surgery , Liver Neoplasms/therapy , Colorectal Neoplasms/pathology , Hepatectomy , Humans , Liver Neoplasms/secondary , Retrospective Studies , Treatment OutcomeABSTRACT
The Enhancer of Zeste homologue2 gene (EZH2) is frequently expressed at high levels in malignant tumours, including bladder cancer. It functions as a transcriptional regulator to the maintenance of cell identity, cell cycle regulation and oncogenesis. In the study, we detected EZH2 expression in bladder cancer tissues. These results showed EZH2 high expression in bladder cancer tissue at level of transcript and protein compared with normal bladder tissue and EZH2 expression correlated positively with tumour stage and grade. Then, we used RNA interference to inhibit EZH2 expression in bladder cancer EJ cell line. Efficient downregulation of EZH2 resulted in significantly decreased cell proliferation in EJ cells and retarded transition of G(1) phase to S phase. Our data suggest that EZH2 is involved in the tumourigenesis of bladder cancer and EZH2 downregulation contributes to inhibiting malignant growth by retarding cell entrance to S phase.
Subject(s)
Cell Proliferation , DNA-Binding Proteins/genetics , Neoplasm Proteins/genetics , RNA Interference , Transcription Factors/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Aged , Blotting, Western , Cell Line, Tumor , DNA-Binding Proteins/metabolism , Down-Regulation , Enhancer of Zeste Homolog 2 Protein , Female , Flow Cytometry , G1 Phase , Gene Expression Regulation , Humans , Male , Middle Aged , Neoplasm Proteins/metabolism , Polycomb Repressive Complex 2 , Polymerase Chain Reaction , RNA, Messenger/metabolism , Transcription Factors/metabolism , Urinary Bladder Neoplasms/metabolismABSTRACT
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.
