RESUMO
Background: Accumulating evidence suggests an antineoplastic role of MicroRNA-34a (miR-34a) in human cancer. However, its precise biological functions stay largely elusive. Purpose: Our study was aimed to investigate the impact of miR-34a on hepatocellular carcinoma (HCC) and its underlying apoptosis related mechanisms in vitro, as well as the association of miR-34a, E2F1 and E2F3 expression with patient survival of HCC using publicly accessed datasets. Methods: The HBV-expressing Hep3B and SNU-449 cell lines with or without enforced expression of miR-34a were in vitro cultured for cell proliferation, colony formation, wound healing, cell invasion, and 3D spheroid formation. Quantitative reverse transcription PCR (RT-qPCR) was performed for E2F1, E2F3 expression. Caspase-3 (CASP3) activity was determined using a CaspACETM Assay System. Kaplan-Meier survival curves were used to analyze the associations of miR-34a, E2F1 and E2F3 expression and overall survival in HCC. Meta-analysis was performed to examine the differential expression of E2F1 and E2F3 between primary HCC vs normal tissues. Results: The results in vitro showed that enforced miR-34a expression significantly inhibited cell proliferation, migration, and invasion of both Hep3B and SNU-449. RT-qPCR results demonstrated that miR-34a could significantly suppress E2F1 and E2F3 expression, particularly in SNU-449. CASP3 activity in both Hep3B and SNU-449 increased in miR-34a treatment group. Overexpressed E2F1 and E2F3 were observed in primary HCC vs normal tissues. Survival analyses showed that HCC patients with either high miR-34a, or low E2F1, or low E2F3 expression had better survival than their opposite counterparts, respectively. Conclusion: Our study suggested thatmiR-34a can modulate the expression of E2F1, E2F3, and CASP3 activity, thereby repressing tumor aggressiveness and expediting apoptosis in liver cancer cells.
RESUMO
Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.
