Sodium Butyrate Upregulates miR-203 Expression to Exert Anti-Proliferation Effect on Colorectal Cancer Cells

Background/Aims: Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes and cancer progression. Whether lncRNAs play any functional role in colorectal carcinoma (CRC) remains largely unknown. The aim of this study was to investigate the role of lncRNA CPS1 intronic transcript 1 (CPS1-IT1) in CRC. Methods: Expression of CPS1-IT1 was initially assessed in human CRC tissues and in a series of CRC cell lines. The correlations between CPS1-IT1 levels and survival outcomes were analyzed to elucidate the clinical significance of CPS1-IT1 in CRC. The underlying mechanisms of CPS1-IT1 in CRC were analyzed through in vitro and in vivo functional assays. Results: Expression of CPS1-IT1 was significantly decreased in CRC tissues and cell lines, and patients with low CPS1-IT1 expression had poor survival outcomes. The results of in vitro assays revealed that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities and accelerated cell apoptosis, thereby suppressing epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor-suppressive role of CPS1-IT1. Conclusion: In this study, we found that CPS1-IT1 has a tumor-suppressive role in CRC. Our data suggest that CPS1-IT1 could be used as a new prognostic biomarker and therapeutic target for CRC.

Section: Introductionmentioning

confidence: 99%

LncRna CPS1-IT1 Suppresses Cell Proliferation, Invasion and Metastasis in Colorectal Cancer

Zhang¹,

Yuan²,

Song³

et al. 2017

“…Through these post-transcriptional gene regulation mechanisms, miRNAs regulate a wide range of biological processes, including cell apoptosis and differentiation, migration, apoptosis, development and metabolism [13-15]. Accumulating evidence has shown aberrant miR-520 expression in tissue samples from with many types of human malignant tumours [16].…”

Section: Introductionmentioning

confidence: 99%

A Novel Role for MiR-520a-3p in Regulating EGFR Expression in Colorectal Cancer

Zhang

Liu

et al. 2017

Background/Aims: MicroRNAs (miRNAs) have been consistently demonstrated to be involved in colorectal cancer as either tumour oncogenes or tumour suppressors. However, the detailed role of miR-520a-3p in colorectal cancer remains poorly understood. Methods: Quantitative RT-PCR and western blotting assays were used to measure miR-520a-3p and EGFR expression levels in colorectal cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p. Cell migration, apoptosis and cell cycle assays were performed to analyse the biological functions of miR-520a-3p and EGFR in colorectal cancer cells. In vivo experiment was performed to analyse the effects of miR-520a-3p and EGFR on the growth of colorectal cancer xenografts in mice. Results: In this study, we found that miR-520a-3p was most likely to target the EGFR 3’-UTR, which was experimentally validated. In addition, we investigated the biological effects of EGFR inhibition by miR-520a-3p both in vitro and In vivo and found that miR-520a-3p could suppress cell migration, promote apoptosis, lead to colorectal cancer cell cycle arrest at the G0/G1 phase, and decelerate tumour growth in xenograft mice, potentially by targeting EGFR. Conclusions: This study highlights a tumour suppressor role for miR-520a-3p in colorectal cancer via the regulation of EGFR expression. Thus, miR-520a-3p may be a novel molecular therapeutic target for colorectal cancer.

“…All those ultrastructural changes could be related to the first stage of an apoptotic process which may suggest a transition between the two types of programmed cell death: apoptosis or autophagy. Additional experiments with a positive control for apoptosis [39] would be interesting to further corroborate the implication of the apoptotic process.…”

Section: Discussionmentioning

confidence: 99%

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Abal¹,

Louzao²,

Fraga-Corral³

et al. 2017

Background: Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellates genera Azadinium and Amphidoma. These toxins cause azaspiracid poisoning (AZP), characterized by severe gastrointestinal illness in humans after the consumption of bivalve molluscs contaminated with AZAs. The main aim of the present study was to examine the consequences of human exposure to AZA1 by the study of absorption and effects of the toxin on Caco-2 cells, a reliable model of the human intestine. Methods: The ability of AZA1 to cross the human intestinal epithelium has been evaluated by the Caco-2 transepithelial permeability assay. The toxin has been detected and quantified using a microsphere-based immunoassay. Cell alterations and ultrastructural effects has been observed with confocal and transmission electron microscopy Results: AZA1 was absorbed by Caco-2 cells in a dose-dependent way without affecting cell viability. However, modifications on occludin distribution detected by confocal microscopy imaging indicated a possible monolayer integrity disruption. Nevertheless, transmission electron microscopy imaging revealed ultrastructural damages at the nucleus and mitochondria with autophagosomes in the cytoplasm, however, tight junctions and microvilli remained unaffected. Conclusion: After the ingestion of molluscs with the AZA1, the toxin will be transported through the human intestinal barrier to blood causing damage on epithelial cells.