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Info. Vol.11 - No.4 (2017.12.20)
Title miRNA-mediated Expression Switch of Cell Adhesion Genes Driven by Microcirculation in Chip
Authors Timur R Samatov1,*,??/sup>, Vladimir V Galatenko2,3, Nadezhda V Senyavina4, Alexey V Galatenko2, Maxim Yu Shkurnikov5, Svetlana A Tonevitskaya1, Dmitry A Sakharov1,4, Uwe Marx6, Hermann Ehrlich7, Udo Schumacher8 & Alexander G Tonevitsky5,*
Institutions 1Moscow State University of Mechanical Engineering, Bolshaya Semenovskaya str 38, 107023 Moscow, Russia
2Moscow State University, Leninskie Gory, 119991 Moscow, Russia
3National Research University Higher School of Economics, Kochnovsky Pass 3, 125319 Moscow, Russia
4SRC Bioclinicum, Ugreshskaya str 2/85, 115088, Moscow, Russia
5P. Hertsen Moscow Oncology Research Institute, National Center of Medical Radiological Research, 3 Second Botkinsky Lane, Moscow, 125284, Russia
6TissUse GmbH, Oudenarder Strasse 16, 13347 Berlin, Germany
7Institute of Experimental Physics, TU Bergakademie Freiberg, Leipziger Stra횩e 23, 09599 Freiberg, Germany
8Department of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg D-20246, Germany
??/sup>Present address Evotec International GmbH, Marie-Curie-Str. 7, 37079, G철ttingen, Germany
*Correspondence and requests for materials should be addressed to T.R. Samatov (t.samatov@bioclinicum.com) and A.G. Tonevitsky (tonevitsky@mail.ru)
Abstract 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 Transwell짰 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.
Keyword CaCo2 cell line, Microfluidic chip, Microarray analysis, Cell adhesion, mRNA-miRNA network
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