ABSTRACT
Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)
Subject(s)
Humans , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/metabolism , HMGB2 Protein/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Cell Line, Tumor , Cell Movement/genetics , Neoplasm Invasiveness/genetics , Nuclear Proteins/metabolism , /genetics , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
OBJECTIVE: Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. METHOD: Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. RESULTS: HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. CONCLUSION: Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC.
Subject(s)
Carcinoma, Adenoid Cystic , MicroRNAs , Salivary Gland Neoplasms , Humans , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/metabolism , Carcinoma, Adenoid Cystic/pathology , RNA, Circular/genetics , HMGB2 Protein/genetics , HMGB2 Protein/metabolism , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/pathology , Transcription Factors/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Line, Tumor , Neoplasm Invasiveness/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Cell Proliferation , Nuclear Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
BACKGROUND: Caffeine has an anti-obesity effect, although chronic excessive caffeine consumption also causes caffeinism, which is marked by increased anxiety or depression, amongst other symptoms. The present study aimed to investigate whether the addition of flavonoids such as astilbin can reduce the caffeine dose needed to inhibit obesity. RESULTS: ICR mice (n = 80) were fed with normal diet, high-fat diet (HFD), HFD supplemented with astilbin, caffeine, or astilbin + caffeine for 12 weeks. When diets supplemented with astilbin, 0.3 g kg-1 diet caffeine had the same effect as 0.6 g kg-1 diet caffeine alone, and 0.6 g kg-1 diet caffeine combined with astilbin most effectively inhibited HFD-induced obesity. Astilbin improved the anti-obesity effects of caffeine on lipid accumulation via the activation of AMP-activated protein kinase α (AMPKα). (i) Activated AMPKα decreased lipid biosynthesis by suppressing the activity or mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein 1c and its target gene fatty acid synthase. (ii) Activated AMPKα also up-regulated lipolysis by enhancing the expression of adipose triglyceride lipase and increasing the phosphorylation of hormone-sensitive lipase. (iii) Finally, activated AMPKα increased carnitine acyltransferase and acyl-CoA oxidase activities, which further promoted fatty acid ß-oxidation. CONCLUSION: The results obtained in the present study indicate that astilbin may decrease the effective dose of caffeine needed for an anti-obesity effect and also suggest that it suppresses fat accumulation via the activation of AMPK. © 2020 Society of Chemical Industry.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Anti-Obesity Agents/administration & dosage , Caffeine/administration & dosage , Flavonols/administration & dosage , Lipid Metabolism/drug effects , Obesity/drug therapy , AMP-Activated Protein Kinases/genetics , Animals , Anti-Obesity Agents/antagonists & inhibitors , Caffeine/antagonists & inhibitors , Diet, High-Fat/adverse effects , Dietary Supplements/analysis , Humans , Lipogenesis/drug effects , Lipolysis/drug effects , Male , Mice , Mice, Inbred ICR , Mice, Obese , Obesity/genetics , Obesity/metabolism , Obesity/physiopathology , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolismABSTRACT
In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD), and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT) weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK), carnitine acyltransferase (CAT) and hormone-sensitive lipase (HSL) were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2) was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.
