Background. Liver hepatocellular carcinoma (LIHC) has had a continuous increase in incidence and mortality rates over the last 40 years. Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) is a protein coding gene which encodes the cytoplasmic dynein heavy chain family. This is the first investigation into the expression of DYNC1H1 and its mechanisms of action in LIHC patients. Methods. Based on the DYNC1H1 expression data from the TCGA database, we performed the DYNC1H1 expression, clinicopathological data, gene enrichment, and immune infiltration analysis. TIMER and CIBERSORT were used to assess immune responses of DYNC1H1 in LIHC. GEPIA, K-M survival analysis, and immunohistochemical staining pictures from the THPA were used to validate the results. In order to evaluate the diagnostic value of DYNC1H1, GEO datasets were analyzed by using ROC analysis. And quantitative real-time polymerase chain reaction was also carried out to evaluate the expression of DYNC1H1. Results. DYNC1H1 expression levels were associated with T classification, pathologic stage, histologic grade, and serum AFP levels. DYNC1H1 is an independent factor for a poor prognosis in patients with LIHC. Further study showed that high expression of DYNC1H1 was enriched in epithelial–mesenchymal transition (EMT) and the TGF β signaling pathway by GSEA analysis enrichment, indicating that DYNC1H1 might play a key role in the progression of CRC through EMT and immune response, which also had been validated by the experimental assays. Conclusions. DYNC1H1 will provide a novel and important perspective for the mechanisms of LIHC by regulating EMT. This gene will be able to act as an efficacious tool for the early diagnosis and effective intervention of LIHC.
Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/β-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis.
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