Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via β-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.
Helicobacter pylori (H. pylori) infects nearly half of the global population and is recognized as one of the most common chronic bacterial infections worldwide. 1 Research on H. pylori has shown that it is not only a risk factor for digestive diseases, such as gastrointestinal ulcer, chronic gastritis, and gastric cancer, but also exerts a certain influence on various extra-digestive diseases, including non-alcoholic fatty liver, diabetes mellitus, and cardiovascular diseases. 2 Studies have also shown that eradication of H. pylori can effectively reduce the incidence and
Head and neck squamous cell carcinoma (HNSCC) is one of the most malignant cancers with poor prognosis worldwide. Emerging evidence indicates that competing endogenous RNAs (ceRNAs) are involved in various diseases, however, the regulatory mechanisms of ceRNAs underlying HNSCC remain unclear. In this study, we retrieved differentially expressed long non-coding RNAs (DElncRNAs), messenger RNAs (DEmRNAs) and microRANs (DEmiRNAs) from The Cancer Genome Atlas database and constructed a ceRNA-based risk model in HNSCC by integrated bioinformatics approaches. Functional enrichment analyses showed that DEmRNAs might be involved in extracellular matrix related biological processes, and protein–protein interaction network further selected out prognostic genes, including MYL1 and ACTN2. Importantly, co-expressed RNAs identified by weighted co-expression gene network analysis constructed the ceRNA networks. Moreover, AC114730.3, AC136375.3, LAT and RYR3 were highly correlated to overall survival of HNSCC by Kaplan–Meier method and univariate Cox regression analysis, which were subsequently implemented multivariate Cox regression analysis to build the risk model. Our study provides a deeper understanding of ceRNAs on the regulatory mechanisms, which will facilitate the expansion of the roles on the ceRNAs in the tumorigenesis, development and treatment of HNSCC.
The present study showed a high rate of discordance in matched pairs of primary tumors and metastases, suggesting that the accurate evaluation of HER2 status is essential before any therapeutic decision.
Peritoneal metastasis from colorectal cancer (CRC) is related to poor prognosis. Intraperitoneal chemotherapy is an efficient method to treat peritoneal metastasis (PM); however, the outcomes remain unsatisfactory. The present study aimed to investigate the antitumor activity of lobaplatin and its role in intraperitoneal chemotherapy. The findings showed that the proliferation of CRC was inhibited in a dose-dependent manner when DLD1 and HCT116 cells were treated with various concentrations of lobaplatin (0, 6.3, 12.5, 25, 50, and 100 μg/mL, respectively). Flow cytometry and Western blot analysis confirmed that lobaplatin affected CRC cells by inducing apoptosis and modulating the caspase family. In the animal study, nude mice were injected with DLD1 cells and divided into three groups. Lobaplatin was injected intraperitoneally to simulate intraperitoneal chemotherapy. Group A was the control group treated with PBS. Group B was injected with DLD1 and treated with lobaplatin simultaneously, while group C was treated with lobaplatin 1 week after cell injection. The results showed that group A harbored maximal tumors on the peritoneal surface, while group B had the least number (9.2 ± 1.3 and 0.4 ± 0.5, respectively P < 0.01). These findings indicated that lobaplatin suppressed the tumor growth as an intraperitoneal chemotherapy agent and achieved a satisfactory therapeutic effect at an early stage. Further blood test and tissue staining did not reveal any liver and kidney toxicity that was induced by lobaplatin. In conclusion, lobaplatin could be an effective and safe agent for CRC treatment, thereby commissioning a novel strategy in intraperitoneal chemotherapy for patients with peritoneal metastasis.
In the current era of precision medicine, there is a general consensus that the anatomical site is an important factor in the management of colorectal cancer (CRC). To investigate the underlying molecular mechanisms between proximal and distal CRC and to identify the responsible genes, we analyzed the gene expression patterns of colorectal tumors from two microarray datasets, GSE39582 and GSE14333, on the NCBI Gene Expression Omnibus and the RNA-seq data from TCGA. Weighted coexpression network analysis (WGCNA) was applied to construct a gene coexpression network. The red module in GSE39582 and the dark-gray module from the TCGA dataset were found to be highly correlated with the anatomical site of CRC. A total of 12 hub genes were found in two datasets, 2 of which PLAG1 like zinc finger 2 (PLAGL2) and protein O-fucosyltransferase 1 (POFUT1) were common and upregulated in tumor samples in CRC. The module with the highest correlation provided references that will help to characterize the difference between left-sided and right-sided CRC. The survival analysis of PLAGL2 and POFUT1 expression revealed differences between proximal and distal CRC. Gene set enrichment analysis based on those two genes provided similar results: GPI anchor biosynthesis and peroxisome and selenoamino acid metabolism. PLAGL2 and POFUT1, which have the highest correlation with tumor location, may serve as biomarkers and therapeutic targets for the precise diagnosis and treatment of CRC in the future.
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