miR-23a-induced HCC cell hypersensitivity to 5-Fu treatment requires TOP2A. A shows that miR-23a fails to potentiate HCC cells to 5-Fu treatment. HepG2 and MHCC97L cells with or without expressing ectopic miR-23a were treated with etoposide for 24 and 48 h. Cytotoxicity was evaluated with MTT assay. No different cytotoxicity was observed in miR-23a-overexpressed cells in compared with wild-type cells. B shows that miR-23a could not enhance chemotoxocity of 5-Fu in vivo. Methodologies were described as Figure 1C and D and mice were treated with 5-Fu (25 mg/kg/2 days, i.p.). Neither delayed presence of megascopic xenograft nor reduced tumor size could be observed in miR-23a-overexpressed group. This picture presents the 3 representatives in each group. C shows that miR-23a suppresses TOP1 expression without significantly inducing TOP2A in HCC cells. Wild-type and miR-23a-overexpressed HCC cells were treated with etoposide (20 μM) or 5-Fu (50 μg/mL) for 24 h then protein was collected. The expression of TOP1 and TOP2A was analyzed with immunoblotting. Significant reduction of TOP1 expression in miR-23a overexpressed HCC cells could be observed. No potent up-regulation of TOP2A could be found. D shows that overexpression of miR-23a further impaired cell progression through S phase in etoposide-treated HCC cells. Wildtype and miR-23a-overexpressed HCC cells were treated with etoposide (20 μM) for 24 h and then fixed. Cells were then stained with PI for cell cycle analysis. Accumulation at S phase was observed after etoposide treatment and ectopic miR-23a enhances this effect of etoposide. *p < 0.05; p < 0.01 in comparison.