Project description:Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is characterized as a highly aggressive tumor entity and has become a health challenge worldwide. Intracellular secreted protein acidic and rich in cysteine (SPARC) has been described as secreted protein that serves as paracrine mediator between cells extracellular matrix (ECM), however, its intracellular role remains unclear. Genetically modified HCC cell lines, cancer patient-derived organoids, and mouse models were used to analyze SPARC on metabolic processes, as well as the invasive behavior and sorafenib resistance of HCC cells. Transcriptome, interactome, and biochemical analyses were performed to study how SPARC regulate cholesterol homeostasis. High expression of intracellular SPARC was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. Our findings unveil a previously unrecognized interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling serves as a promising strategy for treating advanced HCC.
Project description:Secreted MOdular Calcium-binding protein-2 (SMOC2) belongs to the SPARC (Secreted Protein Acidic and Rich in Cysteines) family of matricellular proteins whose members are known for their secretion into the extracellular space to modulate cell-cell and cel
Project description:Metabolic dysfunction of skeletal muscle is often prevalent at an early stage in the development of several non-communicable diseases. Here, we investigated the effect of a myokine, secreted protein acidic and rich in cysteine (SPARC), on glucose tolerance in human and mouse skeletal muscles. SPARC knockout mice showed marked decreases in parameters for whole-body glucose metabolism, along with reduced phosphorylation of AMPK and Akt in skeletal muscle tissues compared with wild-type mice. Furthermore, mice injected with SPARC showed improved glucose tolerance concomitant with AMPK activation. Exogenous SPARC treatment accelerated glucose uptake in muscle tissues isolated from wild-type mice but not from AMPKγ3 knockout mice. In muscle cells, SPARC increased glucose uptake concomitant with AMPK activation, mediated by a calcium-dependent signal. Chronic treatment of SPARC restored metabolic functions in diet-induced obese mice. These findings suggest that SPARC improves glucose metabolism via AMPK activation in skeletal muscle, providing mechanistic insights on exercise-induced metabolic benefits and physical inactivity-induced glucose intolerance.
Project description:SPARC is a matricellular glycoprotein that plays critical roles in the pathologies associated with obesity and diabetes, as well as tumorigenesis. The objective of this study was to investigate the role of SPARC in the process of trophoblast invasion which shares many similarities with tumor cells invasion. Our results reveals that hormones, cell adhesion molecules, ECM molecules, growth factors and cytokines all are mediated by SPARC in EVT invasion. HTR-8/SVneo cells were transfected with SPARC siRNA or a 25-nucleotide universal negative control siRNA using Lipofectamine 2000 according to the manufacturer’s protocol. Seventy-two hours after transfection, cells were harvested and RNA was isolated using standard procedures.
Project description:MicroRNAs (miRNAs) are small noncoding RNAs that critically regulate gene expression. Their abundance and function have been linked to processes such as senescence and aging. In aged monkey muscle, miR-451a and miR-144-3p were highly upregulated compared to young animals. This led us to hypothesize that the miRNAs 451a/144-3p may be involved in muscle differentiation. We found that these miRNAs are downregulated during the differentiation of C2C12 myoblasts. Overexpression of miR-451a, but not miR-144-3p, robustly impeded the differentiation, suggesting an inhibitory role for miR-451a. We further investigated the potential regulatory targets of miR-451a and identified Sparc mRNA, encoding a secreted protein acidic and rich in cysteine (SPARC), which is involved in wound healing and cellular differentiation. Interestingly, we found that miR-451a suppresses Sparc mRNA translation according to the analysis of polysome profile. Our findings show that miR-451a is downregulated in differentiated myoblasts and decreases C2C12 differentiation at least in part by the suppression of SPARC biosynthesis.
Project description:The goal of this study is to compare miRNAs expressed by HGF treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during HGF-mediated HTR-8/SVneo cells invasion
Project description:The goal of this study is to compare mRNAs expressed by EGF treated HTR-8/SVneo cells to iRNAs expressed in untreated control HTR-8/SVneo cells to identify various genes which play a role during EGF-mediated HTR-8/SVneo cell invasion
Project description:The goal of this study is to compare miRNAs expressed by EGF treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during EGF-mediated HTR-8/SVneo cell invasion
Project description:The goal of this study is to compare miRNAs expressed by IFN-gamma treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during IFN-gamma-mediated HTR-8/SVneo cells invasion
