MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.

BACKGROUND: Matrix metalloproteinases (MMP) are important proteases that degrade the extracellular matrix (ECM) and thus essentially mediate tumor vascularization, metastasis, and invasion. However, their potential roles in uterine corpus endometrial carcinoma (UCEC) are not fully understood. PATIENTS AND METHODS: The expression, prognostic value, and correlation of UCEC patients with MMP were investigated using data from The Cancer Genome Atlas (TCGA) and other databases. Furthermore, differentially expressed genes (DEGs) were identified and their biological functions and correlations with infiltrating immune cells were analyzed. RESULTS: A total of 22 MMPs were found to be abnormally expressed in UCEC tumor tissues, and high expression of MMP11 and MMP17 were associated with a better UCEC prognosis. MMP11 and MMP17 were observed to be significantly enriched in tumor tissue ECM and were associated with pathways involving degradation, glycolytic metabolism, and PI3K-Akt signaling. Infiltration of natural killer (NK), mast, and NK CD56bright cells was enhanced in tumor tissues with high MMP11 and MMP17 expression. CONCLUSION: MMP11 and MMP17 may affect UCEC prognosis by influencing immune cell infiltration and may be potential UCEC biomarkers.

Xiao-Luo-Wan treats propylthiouracil-induced goiter with hypothyroidism in rats through the PI3K-AKT/RAS pathways based on UPLC/MS and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Goiter with hypothyroidism occurs in several thyroid diseases. Xiao-Luo-Wan (XLW), which contains Scrophularia ningpoensis Hemsl., Fritillaria thunbergii Miq. and Ostrea gigas Thunberg, has been used as an effective Chinese medicine for the treatment of goiters in China for hundreds of years. Based on clinical observations and experimental studies, XLW also exerts a certain effect on hypothyroidism. However, the therapeutic mechanism of XLW remains unclear. AIM OF THE STUDY: The present study aimed to investigate the therapeutic effect of XLW on propylthiouracil (PTU)-induced goiter with hypothyroidism in rats and to uncover the underlying molecular mechanism using ultra high-performance liquid chromatography-mass spectrometry (UPLC/MS), network pharmacology, and molecular docking simulations. MATERIALS AND METHODS: After successful modeling, the remaining rats were randomly divided into a model group, an Euthyrox group, an XLW group, and a control group. The corresponding drugs were given by gavage for four consecutive weeks. The growth status was monitored, the relative thyroid weight was calculated, and the total serum T3, T4, and TSH content were detected. Hematoxylin-eosin (H&E) staining was used to observe the pathological changes in the thyroid glands. The chemical components of the XLW were identified by UPLC/MS and the putative targets of XLW were predicted using multiple databases. We performed network pharmacology based on the intersection of goiter/hypothyroidism-related targets and XLW targets. Then, we performed KEGG pathway enrichment analysis, and key targets were further screened using protein-protein interaction (PPI) networks. Finally, molecular docking was used to predict the binding ability of XLW identified components and the key targets. RESULTS: XLW significantly increased the levels of T3 and T4, and reduced TSH, increased body weight, and decreased swollen thyroid glands in PTU-induced rats. XLW promoted the morphological recovery of thyroid follicles and epithelial cells. Twenty-one main chemical components of XLW were identified using UPLC/MS. 270 potential gene targets of XLW and 717 known targets of goiter/hypothyroidism disease were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction, and UniProt databases. A total of 83 KEGG pathways were enriched with phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) and RAS signaling pathways. PPI analysis revealed nine key targets of kinase-protein kinase B (AKT) 1, interleukin (IL) 6, vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), epidermal growth factor receptor (EGFR), GTPase HRas (HRAS), matrix metalloproteinase (MMP) 9, and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Molecular docking verified which drug components had good binding ability to key targets (all ≤5 kcal/mol). CONCLUSION: For PTU-induced goiter with hypothyroidism in rats, XLW improves thyroid function, reduces goiter, increases body weight, and promotes the recovery of thyroid follicles and epithelial cells. The underlying molecular mechanism suggests that XLW may regulate thyroid hormone signaling by regulating the PI3K-AKT, RAS, and other signaling pathways. This study provides a pharmacological and biological basis for using XLW to treat goiter with hypothyroidism.

Upregulation of microRNA-132 in gastric cancer promotes cell proliferation via retinoblastoma 1 targeting.

Gastric cancer is one of the most frequent malignancies and a leading cause of cancer-related mortality worldwide. MicroRNAs (miRs), a class of small non­coding RNAs, have been shown to be critical in tumorigenesis. In the present study, the expression levels of miR­132 were analyzed in gastric cancer samples using quantitative reverse transcription­polymerase chain reaction. In addition, the cell viability, proliferation and invasion abilities were determined in two gastric cancer cell lines, NCI­N87 and MGC80­3, that were transfected with miR­132 mimics or antisense oligos. It was found that miR­132 expression was significantly upregulated in gastric cancer tissues when compared with adjacent non­cancerous tissues. At the molecular level, the data demonstrated that miR­132 inhibits the protein levels of retinoblastoma 1 (RB1) by targeting the 3'­untranslated region. Furthermore, reintroduction of RB1 markedly attenuated the proliferative roles of miR­132 overexpression. Therefore, the present results indicate that the miR­132/RB1 regulatory axis may be a potential novel diagnostic and therapeutic target for the treatment of gastric cancer.