Molecular & Cellular Toxicology最新文献

Background

Colorectal cancer (CRC) is one of the most common malignancies worldwide and a major threat to human life and health. Circular RNA (circRNA)-microRNA (miRNA)-mRNA mechanism is considered to occur in various cancers. However, the mechanism of circ_101692 in CRC is still unclear.

Methods

Quantitative real-time PCR was used to detect the expression of circ_101692, miR-449b-5p and Golgi phosphoprotein 3 (GOLPH3) in CRC tissues and cell lines. Cell proliferation was determined using cell counting kit-8 (CCK8), colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU). Flow cytometry and transwell were performed to measure apoptosis and cell invasion, respectively. Besides, glucose uptake and lactate production were tested using commercial kits to determine the glycolytic of CRC. Furthermore, dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the relationship between miR-449b-5p and circ_101692 or GOLPH3. And the protein levels were monitored using western blot assay. The xenotransplantation model was established to study the role of circ_101692 in vivo.

Results

Circ_101692 and GOLPH3 were highly expressed, while miR-449b-5p expression was down-regulated in CRC tissues and cell lines compared to normal tissues and cell lines. Circ_101692 negatively targeted miR-449b-5p, and GOLPH3 was the downstream gene of miR-449b-5p. Silencing circ_101692 suppressed CRC cell proliferation, invasion and glycolysis, as well as promoted apoptosis, while these influences could be reverted by miR-449b-5p inhibitor. Similarly, overexpression of GOLPH3 abolished the influence of miR-449b-5p mimic on CRC cell behavior. In addition, silencing of circ_101692 restricted CRC tumor growth in vivo.

Conclusion

Our results showed that circ_101692 promoted CRC progression by modulating the miR-449b-5p/GOLPH3 axis, implying that circ_101692 might be a possible target for CRC treatment.

Graphical abstract

Background

Obesity, which is defined as the excess accumulation of body fat, poses metabolic diseases that result in significant health risks. Since conventional anti-obesity medications are known to have significant side effects, we tried a pharmacological approach with a natural product. Ginseng (Panax ginseng) is a traditional Asian medicine that possesses antioxidant, anti-inflammatory, and anti-obesogenic properties. However, the mechanism of the anti-obesity effects of ginseng leaf extract (GLE) is not yet understood.

Objective

We investigated the mechanism by which GLE inhibits the differentiation of 3T3-L1 preadipocytes.

Results

GLE treatment was administered throughout the 8 days differentiation period or at three stages of adipocyte differentiation (early: days 0–2; intermediate: days 2–4; or late: after day 4). During adipocyte differentiation, GLE treatment significantly inhibited 3T3-L1 preadipocyte differentiation at the early stage, leading to a notable reduction in lipid accumulation and a decrease in the expression of crucial adipogenic transcription factors that regulate adipocyte differentiation. GLE also increased the expression of HO-1 and Wnt/β-catenin signaling in a dose-dependent manner during adipocyte differentiation. To evaluate the role of HO-1 induced by GLE, we used HO-1 inhibitor SnPP and HO-1 siRNA. Attenuation of HO-1 function and expression inhibited the decrease in lipid accumulation and adipogenic transcription factor expression caused by GLE; furthermore, inhibition of HO-1 suppressed Wnt/β-catenin signaling.

Conclusions

Overall, our results suggest that GLE inhibits the differentiation of 3T3-L1 preadipocytes by regulating HO-1 expression and Wnt/β-catenin signaling. Therefore, GLE could have preventive uses as a natural product for the treatment of obesity.