ABSTRACT
Purpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures. Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City's permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence. Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83±7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03-1.06), hypertension (OR=2.22, 95% CI:1.71-2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58-4.85), overweight (OR=1.73, 95% CI: 1.20-2.48), high total cholesterol (OR=1.17, 95% CI:1.09-1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00-1.40) and serum insulin (OR=1.05, 95% CI:1.03-1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36-0.84) was found to be inversely related to T2DM development. Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.
ABSTRACT
BACKGROUND: Matrine has been identified to have anticancer activity in hepatocellular carcinoma (HCC). Circ_0055976 was highly expressed in HCC. Here, we investigated the function and relationship of Matrine and circ_0055976 in HCC tumorigenesis. METHODS: Cell proliferation and invasion were detected using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and transwell assays, respectively. Cell aerobic glycolysis was evaluated by detecting glucose consumption, lactate production, and the ratios of ATP/ADP. Levels of genes and proteins were detected by quantitative real-time polymerase chain reaction and Western blotting. The target relationship between miR-1179 and circ_0055976 or lactate dehydrogenase A (LDHA) was analyzed by dual-luciferase reporter assay. The mouse xenograft model was established to conduct the in vivo assay. RESULTS: Matrine suppressed HCC cell proliferation, invasion and anaerobic glycolysis in vitro. Circ_0055976 was highly expressed in HCC tissues and cells, and was reduced by Matrine treatment. Moreover, overexpression of circ_0055976 reversed the anticancer effects of Matrine in HCC cells. Mechanistically, circ_0055976/miR-1179/LDHA formed an axis. Circ_0055976 knockdown or miR-1179 overexpression impaired HCC cell proliferation, invasion, and anaerobic glycolysis, which were reversed by miR-1179 inhibition or LDHA overexpression. Meanwhile, forced expression of LDHA abolished the regulatory effects of Matrine on HCC cells. In the clinic, Matrine impeded HCC tumor growth in vivo, and this effect was boosted after circ_0055976 silencing. CONCLUSION: Matrine suppressed HCC cell proliferation, invasion, and anaerobic glycolysis via circ_0055976/miR-1179/LDHA axis, providing a new insight into the clinical application of Matrine in HCC treatment.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Humans , Animals , Mice , Lactate Dehydrogenase 5 , Matrines , Cell Transformation, Neoplastic , Carcinogenesis , Cell Proliferation , Disease Models, Animal , Cell Line, TumorABSTRACT
Matrine, an effective component extracted from the traditional Chinese herb, Sophora flavescens, has been indicated to exert antitumor activity in different types of cancer. However, the role and precise mechanism of matrine in the progression of liver cancer remains largely unclear. Cell viability, cell proliferation, cell apoptosis, and Warburg effect were estimated by cell counting kit-8 assay, colony formation assay, flow cytometry assay, and glucose uptake and lactate production assay, respectively. The candidate Circular RNAs (circRNAs) were screened by integrating the Gene Expression Omnibus database (GSE155949) analysis with the online program GEO2R. A quantitative real-time polymerase chain reaction was employed to test the expression of circRNA circROBO1, microRNA miR-130a-5p, and roundabout homolog 1 (ROBO1). The interaction of circROBO1/miR-130a-5p/ROBO1 axis was predicted and confirmed by bioinformatics analysis, a dual-luciferase reporter assay, and an RNA pull-down assay. A xenograft mouse model was employed to reveal the role of matrine in vivo. Matrine repressed liver cancer cell viability, proliferation, and Warburg effect, but increased cell apoptosis in vitro. CircROBO1 and ROBO1 were upregulated, but miR-130a-5p was downregulated in liver cancer tissues. Additionally, matrine could reduce the expression of circROBO1 and ROBO1, and increase the expression of miR-130a-5p. Mechanically, overexpression of circROBO1 partly recovered the effect of matrine on liver cancer cell viability, proliferation, apoptosis, and Warburg effect by regulating the miR-130a-5p/ROBO1 axis. Matrine impeded liver cancer development by mediating the circROBO1/miR-130a-5p/ROBO1 axis, which provided a theoretical basis for the application of matrine as an effective anticancer drug for liver cancer.
ABSTRACT
BACKGROUND: Previous studies have shown the anticancer effect of Matrine on hepatocellular carcinoma (HCC); however, the underlying mechanism is still indistinct. METHODS: The expression of circular RNA_0013290 (circ_0013290), microRNA-139-5p (miR-139-5p), matrix metallopeptidase 16 (MMP16), CyclinD1 and N-cadherin was analyzed by quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry assay. Cell viability, proliferation, apoptosis, invasion and tube formation were analyzed by cell counting kit-8, 5-Ethynyl-2'-deoxyuridine, flow cytometry analysis, transwell invasion and tube formation assays, respectively. The associations among circ_0013290, miR-139-5p and MMP16 were predicted by starbase online database, and identified by dual-luciferase reporter and RNA pull-down assays. A xenograft mouse model assay was conducted to disclose the effects of circ_0013290 and Matrine on tumor tumorigenesis in vivo. RESULTS: Circ_0013290 and MMP16 expression were significantly upregulated, while miR-139-5p was downregulated in HCC tissues and cells compared with the matched normal liver tissues and cells. Matrine treatment inhibited HCC cell proliferation, invasion and tube formation but induced cell apoptosis, accompanied by the decrease of CyclinD1 and N-cadherin expression; however, these effects were counteracted when circ_0013290 expression was increased. MiR-139-5p depletion or MMP16 introduction relieved Matrine-induced effects in HCC cells. The regulation of circ_0013290 toward HCC cell processes involved MMP16. With respect to the mechanism, circ_0013290 acted as a miR-139-5p sponge, and miR-139-5p targeted MMP16 in HCC cells. Besides, circ_0013290 regulated MMP16 expression through miR-139-5p. Further, circ_0013290 depletion enhanced the inhibitory effects of Matrine on tumor tumorigenesis. CONCLUSION: Matrine inhibited HCC cell malignancy through the circ_0013290/miR-139-5p/MMP16 pathway, suggesting that Matrine is a potential therapeutic agent for HCC.