Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a
Fig 4
Downregulation of DDC expression by treatment with ibrutinib, LFM-A13, and withaferin-A.
(A) Schematic illustration of similar gene expression signatures between DDC shRNA and chemical compounds. (B) We queried the DDC shRNA gene signature via LINCS database and found BTK inhibitor (LFM-A13), withaferin A, and several compounds shared similar gene expression profiles with DDC shRNA gene signature. Score_best4 and score_best6 are the mean connectivity scores across the four and six cell lines, respectively, in which the perturbagen connected most strongly to the query (DDC shRNA). (C, D, E) DDC, P-BTK, and BTK were upregulated in liver tissues from mir-122 knockout mice. (F) Huh7 cells were treated with various concentrations of ibrutinib, LFM-A13, and withaferin-A for 24–72 hours, respectively. Huh7 cells were treated with (G) 10 and 20 μM ibrutinib or 5 μM sorafenib, (H) 5–20 μM LFM-A13, and (I) 1 and 2 μM withaferin A or 5 μM sorafenib for 24 hours. Cell lysates were subjected to western blot analysis. DDC was downregulated by the treatment of 20 μM ibrutinib and 2 μM withaferin A, but not the treatment of sorafenib. Both DDC and BTK were downregulated by the treatment of LFM-A13 in Huh7 cells.