Although the roles of long non-coding RNA (lncRNA) ANRIL (Antisense non-coding RNA in the INK4A locus) have been established in various tumors, its roles in mitochondrial metabolic reprogramming of hepatocellular carcinoma (HCC) cells are still unclear. This work aims to explore lncRNA ANRIL roles in regulating the mitochondrial metabolic reprogramming of liver cancer cells. First, we found that lncRAN ANRIL expression was significantly increased in HCC tissues or cells compared with the normal adjacent tissues and normal tissues or cells. Functional experiment showed that overexpression of lncRNA ANRIL promoted mitochondrial function in HCC cells, evident by the increased mitochondrial DNA copy numbers, ATP (Adenosine triphosphate) level, mitochondrial membrane potential, and the expression levels of mitochondrial markers, while ANRIL knockdown exerted the opposite effects. Mechanistically, lncRNA ANRIL acted as a competing endogenous RNA to increase ARL2 (ADP-ribosylationfactor-like 2) expression via sponging miR-199a-5p. Notably, the miR-199a-5p/ARL2 axis is necessary for ANRIL-mediated promoting effects on HCC cell mitochondrial function. This work reveals a novel ANRIL-miR-199a-5p-ARL2 axis in HCC cell progression, which might provide potential targets for HCC treatment. K E Y W O R D SANRIL, ARL2, ceRNA, hepatocellular carcinoma, lncRNA, miR-199a-5p
Non-alcoholic fatty liver disease (NAFLd) is one of the most common chronic liver diseases worldwide. Increasing evidence has shown that microRNAs (miRNAs) play a vital role in the progression of NAFLd. The aim of the present study was to examine the expression level and roles of miR-146a in fatty liver of high-fat diet (HFd) and ob/ob mice and fatty acid-treated hepatic cells using RT-qPcR and western blot analysis. The results showed that the expression of miR-146a was significantly decreased in the livers of high-fat diet (HFd) and ob/ob mice and free fatty acid-stimulated cells by RT-qPcR. Overexpression of hepatic miR-146a improved glucose and insulin tolerance as well as lipid accumulation in the liver by promoting the oxidative metabolism of fatty acids. In addition, the overexpression of miR-146a increased the amount of mitochondria and promoted mitochondrial respiration in hepatocytes. Similarly, inhibition of miR-146a expression levels significantly reduced mitochondrial numbers in AML12 cells as well as the expression of mitochondrial respiration related genes. Additionally, MEd1 was a direct target of miR-146a and restoring MEd1 abolished the metabolic effects of miR-146a on lipid metabolism and mitochondrial function. Therefore, results of the present study identified a novel function of miR-146a in glucose and lipid metabolism in targeting MEd1, suggesting that miR-146a serves as a potential therapeutic target for metabolic syndrome disease.
Objective. Gastric cancer is among the most common malignant tumors of the digestive system. This study explored the molecular mechanisms and potential therapeutic targets for gastric cancer occurrence and progression using bioinformatics. Methods. The gastric cancer microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. The R package was used for data mining and screening differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Based on the protein-protein interaction (PPI) network analysis, core targets and core subsets were screened. Then, the relationship between the expression level of the core genes and the prognosis of gastric cancer patients was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Results. Using the GSE19826 and GSE54129 datasets, a total of 550 DEGs were identified, including 248 upregulated and 302 downregulated genes. GO and KEGG analyses showed that the upregulated DEGs were mainly enriched in the extracellular matrix (ECM) organization of the biological process (BP), the collagen-containing ECM of cellular component (CC), and the ECM structural constituent of molecular function (MF). DEGs were also enriched in human papillomavirus infections, the focal adhesion pathway, PI3K-Akt signaling pathway, and among others. The downregulated DEGs were mainly enriched in digestion, basal part of the cell, and aldo-keto reductase (NADP) activity. And the above pathways were enriched primarily in the metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, and retinol metabolism. Five core genes, including COL1A2, COL3A1, BGN, FN1, and VCAN, were significantly highly expressed in gastric cancer patients and were associated with poor prognosis. Conclusion. This study identified new potential molecular targets closely related to gastric cancer occurrence and development via mining public data using bioinformatics analysis methods.
Tanshinone IIA (TanIIA) has multiple biological functions and already been clinically used to treat many cardiovascular diseases. TanIIA is a photoactive molecule and can be excited by light to generate 3TanIIA*. Generation of 3TanIIA* by TanIIA photosensitization indicates that TanIIA may serve as a photosensitizer to bring photodynamic damage to organisms. Therefore, human choroidal melanoma MUM‐2B cell was chosen as a superficial tumor model and the photodynamic effect of TanIIA on tumor cells was evaluated in this study. The results showed that TanIIA photosensitization could generate singlet oxygen in noncellular system. MTT, clone formation and wound‐healing assays showed that the survival and migration of MUM‐2B cells could be efficiently inhibited by TanIIA photosensitization. And then, laser confocal microscope and flow cytometry were used to try to elucidate related mechanism. It was found that TanIIA could pass through cellular membrane and preferably accumulate in nucleus. TanIIA photosensitization could efficiently induce cell apoptosis and necrosis, increase intracellular ROS levels, decrease mitochondria membrane potential, and lead to cell cycle arrest in G2/M phase. Our findings indicate that TanIIA photosensitization can exert remarkable toxicity on choroidal melanoma cells.
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