Deregulated expression of microRNA-200b/c and SUZ12, a Polycomb repressive complex 2 subunit, in chemoresistant colorectal cancer cells
KayKay San1, Megan Horita1, Aravinda Ganapathy1, G. Chinnadurai2 and Uthayashanker R. Ezekiel1
1 Department of Clinical Health Sciences, Doisy College of Health Sciences, Saint Louis University, St. Louis, MO, USA
2 Institute for Molecular Virology and Department of Molecular Microbiology and Immunology, Doisy Research Center, School of Medicine, Saint Louis University, St. Louis, MO, USA
Correspondence to:
Uthayashanker R. Ezekiel, email:
Keywords: SUZ12, miR-200, colorectal cancer, chemoresistance, oxaliplatin
Received: August 04, 2017 Accepted: September 09, 2017 Published: September 21, 2017
Abstract
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.
