Deregulated expression of microRNA-200b/c and SUZ12, a Polycomb repressive complex 2 subunit, in chemoresistant colorectal cancer cells
| Autor: | KayKay San, Uthayashanker R. Ezekiel, G. Chinnadurai, Aravinda Ganapathy, Megan Ann Horita |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer colorectal cancer 03 medical and health sciences 0302 clinical medicine microRNA SUZ12 Genetics Carcinoma medicine business.industry oxaliplatin EZH2 chemoresistance miR-200 medicine.disease Primary tumor Oxaliplatin 030104 developmental biology BMI1 030220 oncology & carcinogenesis Cancer research business Research Paper medicine.drug |
| Zdroj: | Genes & Cancer |
| ISSN: | 1947-6027 |
| DOI: | 10.18632/genesandcancer.152 |
| Popis: | In colorectal cancer, chemotherapy and/or radiotherapy can lead to the formation of resistant cells that become metastatic through Epithelial-Mesenchymal Transition (EMT). Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. During EMT, the primary tumor cells lose cell-cell adhesion, have increased intercellular separation, and gain an elongated shape with pseudopodia. There is also dysregulation of Polycomb group proteins (such as BMI1, SUZ12, and EZH2), and changes in the expression of microRNA-200 (miR-200) family. In this study, we developed a chemoresistant colorectal cancer cell line (DLD-1-OxR) by exposing DLD-1 colorectal cancer cells to increasing concentrations of oxaliplatin (a chemotherapy drug used for colorectal cancer), and tested for EMT characteristics. We found that DLD-1-OxR exhibited EMT characteristics by morphologic, biochemical and molecular markers. SUZ12, a Polycomb repressive complex 2 subunit, was upregulated in DLD-1-OxR. The miRNA-200 family members that target SUZ12 were downregulated. Drug resistance is an impediment to chemotherapy and understanding the molecular mechanisms of chemoresistance can lead to its reversal and improvement of chemotherapy outcomes. |
| Databáze: | OpenAIRE |
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