Effect of iron on cholesterol 7α-hydroxylase expression in alcohol-induced hepatic steatosis in mice.

Both iron and lipids are involved in the progression of alcoholic fatty liver disease (AFLD), but the interaction between iron and lipids in AFLD is unclear. Here, we tested the hypothesis that iron regulates the expression of genes involved in lipid metabolism through iron regulatory proteins (IRPs), which interact with the iron-responsive elements (IREs) in the untranslated regions (UTRs) of genes, resulting in lipid accumulation. Using "RNA structure software", we predicted the mRNA secondary structures of more than 100 genes involved in lipid metabolism to investigate whether the IRE structure exists in novel mRNAs. Cholesterol 7α-hydroxylase (Cyp7a1) has an IRE-like stem-loop, a noncanonical IRE structure, in its 3'-UTR. Cyp7a1 expression can be regulated by in vivo and in vitro iron treatment. In addition, the noncanonical IRE motif can efficiently bind both to IRP1 and IRP2. The results indicate that hepatic iron overloading in AFLD mice decreased Cyp7a1 expression and resulted in cholesterol accumulation, providing a new mechanism of iron-regulated gene transcription and translation through the interaction between iron and a noncanonical IRE structure in Cyp7a1 mRNA. This finding has significant implications in studying a proposed mechanism for the regulation of cholesterol homeostasis by an Fe/IRP/noncanonical IRE axis.

Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer.

BACKGROUND: As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer. AIM: To explore the role of centrosome-related genes (CRGs) in colon cancer. METHODS: CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes. RESULTS: A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells. CONCLUSION: We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

[The expression of a novel estrogen receptor, GPR30, in epithelial ovarian carcinoma and its correlation with MMP-9].

The aim of the present study is to investigate the expression of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues were obtained from 39 female patients, including 30 cases of EOC and 9 cases of benign ovarian tumor. Four normal ovary tissues were used as control. Immunohistochemical staining was used to detect the expressions of GPR30 and MMP-9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis were used for statistical analysis. The results showed that GPR30 overexpression rate in EOC cases was significantly higher than those in benign ovarian tumor and normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was significantly higher than that in normal ovary cases, without any difference to that in benign ovarian tumor cases. To demonstrate the relationship between GPR30 and clinicopathological variables of EOC, we further analyzed the pathology type, FIGO stage and age of patients sampled in our study. The analysis showed there were significant differences of GPR30 overexpression rate among various pathology types and different FIGO stages (P<0.05), and no significant difference of both GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest that GPR30 may be involved in the invasion and metastasis of EOC, being a potential index of EOC early diagnosis and malignancy grade prediction.