Fig. 4

Integrated regulatory network and ATF4, CCT3, SLC3A2, and hsa-miR-199a-5p significantly impact TRCs selection. a Pathway enrichment results shown as a functionally grouped network by ClueGO. Functionally related terms are displayed using the same color. Crosstalk genes involved in multiple pathways are proportionally marked with the same color as the related pathway. b An integrated network of networks from membrane protein genes, the WNT pathway and cancer genes. c Images of HeLa cells in 90-Pa fibrin gel after infected with hsa-miR-199a-5p inhibitor or mimic. Scale bar, 50 μm (top); 500 μm (bottom). d, e Colony numbers (d) and sizes (e) affected by hsa-miR-199a-5p mimic or inhibitor at day 1 and day 3. f Expression of selected genes quantified by real-time PCR in HeLa TRCs (90 Pa fibrin gel at day 3) and HeLa 2D cells. g The colony number and size were counted at days 1, 3, and 5 for the silence of ATF4, CCT3, and SLC3A2. NC siRNA is negative control siRNA. Mean ± s.e.m., n = 3 independent experiments except for colony size of e and g where n = 10. *p < 0.05, **p < 0.01, ***p < 0.001; ns not significantly different (Student’s t test)