High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells

Figure 1 Transcription levels of miR-196a in cancer cell lines and human CRC. A: Cancer cell lines SW620, HT29 and Snu16 reveal increased miR-196a levels as compared to the primary colon cancer cell line SW480; B: miR-196a transcription is up-regulated in two of seven cancer samples in comparison to the matching mucosa sample. In contrast, no down-regulation in the respective tumor samples was observed.

Figure 2 In vitro effect of miR-196a in human CRC. Transient miR-196a transfection significantly decreases adhesion, increases migration and invasion but does not impact on proliferation or apoptosis of SW480 colon cancer cells.

Figure 3 Impact of miR-196a on cellular signaling, in vitro chemosensitivity and in vivo induction of lung metastases. A: miR-196a transfection activates the AKT pathway but does not impact on the MEK pathway; B: miR-196a transfection significantly increases chemosensitivity towards oxaliplatin and cisplatin but not towards 5-FU or irinotecan; C: miR-196a significantly promoted growth of lung metastases in a xenograft biosystem after tail-vein injection and 7 wk of incubation.

Figure 4 Dose-dependence of miR-196a promoted effects. A: miR-196a decreases HoxA7, HoxB8, HoxC8 and HoxD8 mRNA levels with a dose-dependent and gene-specific character; B: miR-196a inhibits cancer cell adhesion to plastic covers in a dose-dependent manner; C: Biological features of HoxB8, HoxC8 and HoxD8 as reported in literature. HoxB8 exerts an oncogenic effect, while HoxD8 might have tumor-suppressive relevance. For HoxC8 both, pro-oncogenic and anti-oncogenic features, have been reported.