BackgroundUnderstanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer. In this study, we aim to identify the hub genes and investigate the underlying molecular mechanisms of GC.MethodsTo explore potential therapeutic targets for GC,three expression profiles (, , ) of the genes were extracted from the Gene Expression Omnibus (GEO) database. The GEO2R online tool was applied to screen out differentially expressed genes (DEGs) between GC and normal gastric samples. Database for Annotation, Visualization and Integrated Discovery was applied to perform Gene Ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network of these DEGs was constructed using a STRING online software. The hub genes were identified by the CytoHubba plugin of Cytoscape software. Then, the prognostic value of these identified genes was verified by gastric cancer database derived from Kaplan-Meier plotter platform.ResultsA total of 85 overlapped upregulated genes and 44 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, endodermal cell differentiation, and endoderm formation. Moreover, five KEGG pathways were significantly enriched, including ECM-receptor interaction, amoebiasis, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, protein digestion and absorption. By combining the results of PPI network and CytoHubba, a total of nine hub genes including COL1A1, THBS1, MMP2, CXCL8, FN1, TIMP1, SPARC, COL4A1, and ITGA5 were selected. The Kaplan-Meier plotter database confirmed that overexpression levels of these genes were associated with reduced overall survival, except for THBS1 and CXCL8.ConclusionsOur study suggests that COL1A1, MMP2, FN1, TIMP1, SPARC, COL4A1, and ITGA5 may be potential biomarkers and therapeutic targets for GC. Further study is needed to assess the effect of THBS1 and CXCL8 on GC.

Purpose Ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC) is a serious health issue, but etiopathological factors remain unclear. Aldo-keto reductase 1B10 (AKR1B10) is specifically expressed in the colonic epithelium, but down-regulated in colorectal cancer. This study was aimed to investigate the etiopathogenic role of AKR1B10 in UC and CAC. Experimental design UC and CAC biopsies (paraffin-embedded sections) and frozen tissues were collected to examine AKR1B10 expression. Aldo-keto reductase 1B8 (the ortholog of human AKR1B10) knockout (AKR1B8 −/−) mice were produced to estimate its role in the susceptibility and severity of chronic colitis and associated dysplastic lesions, induced by dextran sulfate sodium (DSS) at a low dose (2%). Genome-wide Exome sequencing was used to profile DNA damage in DSS-induced colitis and tumors. Results AKR1B10 expression was markedly diminished in over 90% of UC and CAC tissues. AKR1B8 deficiency led to reduced lipid synthesis from butyrate and diminished proliferation of colonic epithelial cells. The DSS-treated AKR1B8 −/− mice demonstrated impaired injury repair of colonic epithelium and more severe bleeding, inflammation, and ulceration. These AKR1B8 −/− mice had more severe oxidative stress and DNA damage, and dysplasias were more frequent and at a higher grade in the AKR1B8 −/− mice than in wild type mice. Palpable masses were seen in the AKR1B8 −/− mice only, not in wild type. Conclusion AKR1B8 is a critical protein in the proliferation and injury repair of the colonic epithelium and in the pathogenesis of UC and CAC, being a new etiopathogenic factor of these diseases.

Cancer stem cells (CSCs) play crucial roles in tumor progression, chemo- and radiotherapy resistance, and recurrence. Recent studies on CSCs have advanced understanding of molecular oncology and development of novel therapeutic strategies. This review article updates the hypothesis and paradigm of CSCs with a focus on major signaling pathways and effectors that regulate CSC apoptosis. Selective CSC apoptotic inducers are introduced and their therapeutic potentials are discussed. These include synthetic and natural compounds, antibodies and recombinant proteins, and oligonucleotides.

Curcumin is an anticancer agent, but adverse effects and low bioavailability are its main drawbacks, which drives efforts in chemical modifications of curcumin. This study evaluated antiproliferative activity and cancer cell selectivity of a curcumin derivative, curcumin nicotinate (CN), in which two niacin molecules were introduced. Our data showed that CN effectively inhibited proliferation and clonogenic growth of colon (HCT116), breast (MCF-7) and nasopharyngeal (CNE2, 5-8F and 6-10B) cancer cells with IC50 at 27.7 μM, 73.4 μM, 64.7 μM, 46.3 μM, and 31.2 μM, respectively. In cancer cells, CN induced apoptosis and cell cycle arrest at G2/M phase through a p53-mediated mechanism, where p53 was activated, p21 and pro-apoptotic proteins Bid and Bak were upregulated, and PARP was cleaved. In non-transformed human mammary epithelial cells MCF10A, CN at 50 µM had no cytotoxicity and p53 was not activated, but curcumin at 12.5 µM activated p53 and p21 and inhibited MCF10A cell growth. These data suggest that CN inhibits cell growth and proliferation through p53-mediated apoptosis and cell cycle arrest with cancer cell selectivity.