LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases.

Lipid metabolism is an essential biological process involved in nutrient adjustment, hormone regulation, and lipid homeostasis. An irregular lifestyle and long-term nutrient overload can cause lipid-related diseases, including atherosclerosis, myocardial infarction (MI), obesity, and fatty liver diseases. Thus, novel tools for efficient diagnosis and treatment of dysfunctional lipid metabolism are urgently required. Furthermore, it is known that lncRNAs based regulation like sponging microRNAs (miRNAs) or serving as a reservoir for microRNAs play an essential role in the progression of lipid-related diseases. Accordingly, a better understanding of the regulatory roles of lncRNAs in lipid-related diseases would provide the basis for identifying potential biomarkers and therapeutic targets for lipid-related diseases. This review highlighted the latest advances on the potential biomarkers of lncRNAs in lipid-related diseases and summarised current knowledge on dysregulated lncRNAs and their potential molecular mechanisms. We have also provided novel insights into the underlying mechanisms of lncRNAs which might serve as potential biomarkers and therapeutic targets for lipid-related diseases. The information presented here may be useful for designing future studies and advancing investigations of lncRNAs as biomarkers for diagnosis, prognosis, and therapy of lipid-related diseases.

Anticancer effects of dihydromyricetin on the proliferation, migration, apoptosis and in vivo tumorigenicity of human hepatocellular carcinoma Hep3B cells.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anticancer effect on a variety of malignancies, but its anticancer function of DHM in HCC has been unclear. The aim of this study was designed to investigate the anticancer effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. METHODS: Cultured Hep3B cells were treated with different DHM concentrations, followed by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of BCL-2, Cleaved-caspase 3, Cleaved-caspase 9, BAK, BAX and BAD were validated by western blot. RESULTS: DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC cancers compared to the weights in control and NDP group. CONCLUSIONS: DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

Dihydromyricetin Enhances the Chemo-Sensitivity of Nedaplatin via Regulation of the p53/Bcl-2 Pathway in Hepatocellular Carcinoma Cells.

Chemotherapy is an effective weapon in the battle against cancer. Nedaplatin (NDP) is an improved platinum-containing drug with lower cytotoxicity than other similar drugs. However, the repeated use of NDP results in substantial hepatocyte damage as well as drug resistance in hepatocellular carcinoma (HCC) cases. Therefore, the development of effective chemotherapy strategies that enhance tumor sensitivity to chemotherapeutics and reduce the secondary damage to liver cells is urgently needed. Dihydromyricetin (DHM), a natural flavonoid compound, has been shown to have antitumor activity with no obvious toxicity to normal cells in vitro and in vivo. In this study, DHM and NDP were combined to treat liver cancer cells; we found that DHM functions as a protector of normal cells compared with the use of NDP alone. In addition, the synergy of DHM with NDP enhanced the effect of NDP on the induction of HCC cell apoptosis. We found that the combination caused clear changes in the level of reactive oxygen species (ROS). Furthermore, we demonstrated that the combination of DHM and NDP activated the p53/Bcl-2 signaling pathway, which resulted in mitochondrial dysfunction and induced cell death and growth inhibition in HCC cells.