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miRNA-mediated Expression Switch of Cell Adhesion Genes Driven by Microcirculation in Chip
Timur R Samatov,Vladimir V Galatenko,Nadezhda V Senyavina,Alexey V Galatenko,Maxim Yu Shkurnikov,Svetlana A Tonevitskaya,Dmitry A Sakharov,Uwe Marx,Hermann Ehrlich,Udo Schumacher,Alexander G Tonevitsk 한국바이오칩학회 2017 BioChip Journal Vol.11 No.4
Changes in cell adhesion molecule (CAM) expression and miRNAs regulating them are known to be involved in malignant progression in colon cancer. We investigated expression profiles of CAM genes and non-coding RNAs in CaCo2 colon cancer cells in static culture and under dynamic flow conditions perfused in microfluidic chip emulating physiological microenvironment. We incubated monolayers of CaCo2 cells in Transwell® units either under static conditions or under flow in a microfluidic chip. We identified 7 up-regulated CAM genes (CD44, CDH7, CEACAM5, CEACAM6, CYR61, L1CAM and VCAN), 7 down-regulated genes (COL12A1, FGA, FGB, FGG, GJA1, ITGA5 and LAMA1) and 69 miRNAs targeting them under the influence of microcirculation. The revealed network comprised CAM genes known to interact with each other and 13 miRNAs simultaneously regulating more than one of them. The discovered regulatory network comprising CAM genes and miRNAs is likely involved in normal functioning of intestine epithelium as well as in cancer progression.
Tumour-like Druggable Gene Expression Pattern of CaCo2 Cells in Microfluidic Chip
Timur R Samatov,Nadezhda V Senyavina,Vladimir V Galatenko,Eugene V Trushkin,Svetlana A Tonevitskaya,Dmitriy E Alexandrov,Galina P Shibukhova,Udo Schumacher,Alexander G Tonevitsky 한국바이오칩학회 2016 BioChip Journal Vol.10 No.3
The human-on-chip technology provides an efficient basis for preclinical studies and has potentially a greater predictive power for human drug response than classical 2D cell culture. Here we report the expression profile of druggable genes in the human colon cancer cells CaCo2 in static culture and within a microfluidic chip. We identified gene expression pattern under flow to be closer to the one of CaCo2 primary xenograft tumours as compared to those cells grown without circulation. The obtained results indicate that a microenvironment connected to a circulation within a chip brings the cells closer to in vivo situation. Hence the human-on-chip technology is a more powerful tool for drug development than conventional 2D cell culture.