The altered microRNA profile in andrographolide-induced inhibition of hepatoma tumor growth.

BACKGROUND: MicroRNAs (miRNAs) have been reported to play critical roles in regulating gene expression in tumor development. Natural compound andrographolide (Andro), isolated from medicinal herb Andrographis paniculata, was reported to inhibit hepatoma tumor growth in our previous studies. The present study aims to observe the altered miRNAs profile and related signaling pathways involved in Andro-induced inhibition on hepatoma tumor growth.

RESULTS: The inhibition on hepatoma tumor growth induced by Andro (10mg/kg) was found in a xenograft mouse tumor model in vivo. The results of miRNAs chip analysis showed that the expression of 22 miRNAs was increased, whereas the expression of other 10 miRNAs was decreased after Andro treatment. Further, the increased expression of miR-222-3p, miR-106b-5p, miR-30b-5p, and miR-23a-5p was confirmed in hepatoma Hep3B and SMCC7721 cells in vitro after cells were treated with Andro (50μM) for the indicated time. Functional annotation of the target genes based on the differentially expressed miRNAs demonstrated that the majority of the genes were involved in a variety of signaling pathways, including miRNAs in cancer, mitogen-activated protein kinases (MPAKs), focal adhesion. Furthermore, the expression of 24 target genes (total 31) involved in above signaling pathways based on miRNAs analysis was found to be consistent with the alteration of miRNAs.

CONCLUSIONS: The results demonstrate that Andro alters the expression of miRNAs profile and downstream signals, which may contribute to its inhibition on hepatoma tumor growth.