Background and aimHepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms.MethodsThe gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs). The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for DEGs using the Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction (PPI) network of the DEGs was constructed by Search Tool for the Retrieval of Interacting Genes and visualized by Cytoscape. Moreover, miRecords was used to predict the target genes of DEMs.ResultsIn total, 106 DEGs were screened out in HCC, consisting of 89 upregulated genes and 17 downregulated genes, which were mainly enriched in biological processes associated with oxidation–reduction process. Besides, the Kyoto Encyclopedia of Genes and Genomes pathways including chemical carcinogenesis, drug metabolism-cytochrome P450, tryptophan metabolism, and retinol metabolism were involved. A PPI network was constructed consisting of 105 nodes and 66 edges. A significant module including nine hub genes, ASPM, AURKA, CCNB2, CDKN3, MELK, NCAPG, NUSAP1, PRC1, and TOP2A, was detected from the PPI network by Molecular Complex Detection. The enriched functions were mainly associated with the mitotic cell cycle process, cell division, and mitotic cell cycle. In addition, a total of 21 DEMs were identified, including 9 upregulated and 12 downregulated miRNAs. Interestingly, ZBTB41 was the potential target of seven miRNAs. Finally, the nine hub genes and three miRNA-target genes expression levels were validated by reverse transcription-polymerase chain reaction. The relative expression levels of nine genes (ASPM, AURKA, CDKN3, MELK, NCAPG, PRC1, TOP2A, ZBTB41, and ZNF148) were significantly upregulated in cancer tissues.ConclusionThis study identified the key genes and potential molecular mechanisms underlying the development of HCC, which could provide new insight for HCC interventional strategies.
miR-1 suppresses cell proliferation, invasiveness, metastasis, and progression of ESCC by binding its targeted genes LASP1 and TAGLN2.
Background The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs). Results After careful identification and comparison of the morphology and DNA barcoding of 1630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions. Conclusions The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.
Anoikis resistance is an essential prerequisite for tumor metastasis, but the underlying molecular mechanisms remain unknown. Herein, we report that the oncoprotein hepatitis B X-interacting protein (HBXIP) is prominently upregulated in breast cancer cells following ECM detachment. Altering HBXIP expression can impair the anchorage-independent growth ability of tumor cells. Mechanistically, HBXIP, which binds to Kelch-like ECH-associated protein 1 (Keap1) to activate nuclear factor E2-related factor 2 (Nrf2), contains a cis-acting antioxidant response element (ARE) in the gene promoter and is a target gene of Nrf2. The HBXIP/Nrf2 axis forms a reciprocal positive feedback loop that reinforces the expression and tumor-promoting actions of each protein. In response to ECM detachment, Nrf2 reduces reactive oxygen species (ROS) accumulation, protects the mitochondrial membrane potential and increases cellular ATP, GSH and NADPH levels to maintain breast cancer cell survival. Meanwhile, the reinforcement of HBXIP induced by Nrf2 inhibits JNK1 activation by inhibiting ubiquitin-mediated degradation of Prdx1, which also plays an essential role in promoting ECM-detached cell survival. Furthermore, a strong positive correlation was identified between HBXIP expression and Prdx1 expression in clinical breast cancer tissues and TCGA Pan-Cancer Atlas clinical data of breast invasive carcinoma based on the cBioPortal cancer genomics database. Co-expression of HBXIP and Prdx1 predicts a poor prognosis for breast cancer patients. Collectively, our findings reveal a significant mechanism by which the HBXIP/Nrf2 feedback loop contributes to anoikis resistance by maintaining redox homeostasis and inhibiting JNK1 activation and support the likely therapeutic value of the HBXIP/Nrf2 axis in breast cancer patients.
BackgroundElevated serum uric acid concentrations have been associated with metabolic syndrome. However, only limited information is available on the prevalence of hyperuricaemia in adolescents. Therefore, the aim of our cross-sectional study was to study the prevalence of hyperuricaemia and dietary patterns in adolescents aged 13–16 years living in Yangzhou, China.MethodsAdolescents were asked to complete a 20-item food frequency questionnaire (FFQ) and provide an overnight fasting finger-prick sample. Principal component analysis (PCA) with varimax rotation was used to derive the dietary patterns that might be associated with high uric acid concentrations.ResultsA total of 1070 adolescents were recruited. Of these, 53.6% (n = 574) were females, and 58.5% (n = 625) were within the normal body mass index (BMI) range. The males had a significantly higher serving size and frequency in their weekly food consumption, including meat, poultry, Chinese cereal staple foods and Western-style fast foods, than the females (all p < 0.02). The overall mean serum uric acid concentration and prevalence of hyperuricaemia were 368.6 ± 114.5 μmol/L and 37.9%, respectively. The prevalence of hyperuricaemia was 4.633 times greater among the participants who were overweight and obese than among those who were underweight. On the other hand, the prevalence of hyperuricaemia was 0.694 times lower among the participants who had normal weight than those who were underweight.ConclusionsThe prevalence of hyperuricaemia was relatively high in Chinese adolescents. The prevention of hyperuricaemia measures should be strengthened in adolescents to effectively control for obesity and gout, which tend to persist into adulthood.
Abstract. ) is a cytokine encoded by a tumor suppressor gene of the IL-10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC 50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non-transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC 50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine-123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Furthermore, the activities of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells were suppressed. These results indicated that Mda-7/IL-24 enhanced the sensitivity of B lymphoma cells to chemotherapy agents by altering the expression of multidrug-resistance genes via downregulating GTP-RhoA-ERK signaling pathway, suggesting that treatment of B cell lymphomas with Mda-7/IL-24 could avoid MDR.
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