HOXC10 Overexpression Promotes Cell Proliferation and Migration through Regulation of CST1 Expression in Gastric Cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119196 | GEO | 2019/06/20
REPOSITORIES: GEO
Similar Datasets
Project description:HOXC10 Overexpression Promotes Cell Proliferation and Migration through Regulation of CST1 Expression in Gastric Cancer
| PRJNA488452 | ENA
Project description:Homeodomain‑containing gene 10 (HOXC10) is a member of the homeobox transcription factors that plays an important role in the development of multicellular organisms. HOXC10 is overexpressed in a variety of human cancers, and recent studies have revealed that HOXC10 is upregulated in gastric cancer as well. However, its mechanism of action is not fully understood, thus, the role of HOXC10 was investigated in the present study in human gastric cancer. First, HOXC10 expression was revealed to be significantly increased in gastric cancer tissues compared to normal tissues (TCGA dataset), and HOXC10 upregulation was associated with decreased recurrence‑free survival in gastric cancer patients in a public gene expression dataset. HOXC10 promoted cell proliferation and metastasis in two gastric cancer cell lines (AGS and MKN74). Analyzing TCGA 450K DNA methylation dataset, it was revealed that HOXC10 CpG sites were hypomethylated in gastric cancer tissues. Bisulfite sequencing revealed that CpG sites in the HOXC10 first intronic region were hypomethylated in three gastric cancer tissues, and HOXC10 expression was increased in gastric cancer cell lines (AGS and SNU620) in response to 5‑azacytidine treatment. By RNA‑sequencing of AGS cells with ectopic HOXC10 expression, it was revealed that many genes were upregulated by HOXC10 overexpression. Among them, CST1 was predicted to be a HOXC10 direct target gene via prediction of HOXC10 binding sites from the JASPAR database. A chromatin immunoprecipitation assay revealed that HOXC10 directly bound to CST1 promoter regions. The present study proposes HOXC10 is a potential prognostic marker or therapeutic target in human gastric cancer.
| S-EPMC6549078 | biostudies-literature
Project description:Gastric cancer is still one of the most common cancer types and third leading cause of cancer deaths worldwide. Recent studies have showed that the Hippo signaling pathway plays a critical role in progression of gastric cancer. It is of great importance to demonstrate the regulation of Hippo signaling pathway and the degradation of YAP protein in gastric cancer. In this study, we found that OTUB1 is a critical factor to facilitate gastric cancer cell stemness and progression, which deubiquitinated and stabilized YAP protein.
2022-02-24 | GSE197135 | GEO
Project description:HOXC10 is a member of the HOX family and participates in the regulation of malignant biological behaviors such as growth, migration, and invasion of tumor cells by binding to target genes. ChIP-seq is a powerful tool for studying the interaction between proteins and DNA in the study. Therefore, we use the ChIP-seq method to explore the potential regulatory genes and nucleic acids of HOXC10 in gastric cancer cells.
2022-04-01 | GSE148469 | GEO
Project description:Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human disorders such as developmental diseases. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. In the present study, we used clinical samples from gastric cancer (GC) patients to investigate potential roles of CPXM2 in GC. We also analyzed datasets from the Oncomine database, The Cancer Genome Atlas (TCGA), and the Kaplan‑Meier Plotter to validate these results. We found that CPXM2 was overexpressed in GC and that the overexpression was associated with an unfavorable prognosis, regardless of the Lauren classification and tumor node metastasis staging. In addition, knockdown of CPXM2 in cultured GC cells significantly impeded cell proliferation and migration, as indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. Furthermore, gene set enrichment analysis using RNA‑seq data from TCGA indicated that high CPXM2 expression in GC patients was positively correlated with the HALLMARK_APICAL_JUNCTION and HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION gene sets. Finally, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition were regulated by CPXM2. Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in GCs.
| S-EPMC6718098 | biostudies-literature
Project description:Background:Dysregulation of Rab18 has been implicated in human cancers. However, its clinical significance and biological function in gastric cancer have not been investigated. Methods:We examined Rab18 expression in gastric cancer tissues using immunohistochemistry. We used SNU-1 and AGS cell lines for plasmid and siRNA transfection respectively. MTT, colony formation assay, cell cycle analysis, matrigel invasion, wound healing assay, AnnexinV/PI analysis and western blotting were used to examine the biological effect and mechanism of Rab18 in gastric cancer cell lines. Results:Rab18 protein expression was upregulated in gastric cancer tissues and this correlated with advanced stage and poor prognosis. Rab18 overexpression promoted proliferation in vitro and in vivo. Cell cycle analysis showed that Rab18 overexpression upregulated, while its depletion downregulated S phase percentage. Matrigel invasion and wound healing assays indicated that Rab18 positively regulated SNU-1 cell invasion and migration while its knockdown inhibited AGS cell invasion and migration. Rab18 maintained cell viability and downregulated apoptosis after cisplatin treatment, with upregulated mitochondrial membrane potential and downregulated mitochondrial reactive oxygen species (ROS) production. Rab18 overexpression upregulated p-Rb, survivin while downregulated cytochrome c, cleaved caspase-3 and cleaved PARP. Conclusion:In conclusion, our results indicate that Rab18 promoted gastric cancer growth and chemoresistance, possibly through regulation of mitochondrial function and survivin.
| S-EPMC6225851 | biostudies-other
Project description:The identification of biomarkers and effective therapeutic targets for gastric cancer (GC), the most common cause of cancer-related deaths around the world, is currently a major focus area in research. Here, we examined the utility of Neuronal Regeneration Related Protein (NREP) as a prognostic biomarker and therapeutic target for GC. We assessed the clinical relevance, function, and molecular role of NREP in GC using bioinformatics analysis and experimental validation. Our results showed that in GC, NREP overexpression was significantly associated with a poor prognosis. Our findings also suggested that NREP may be involved in the activation of cancer-associated fibroblasts and the epithelial-mesenchymal transition (EMT), with transforming growth factor β1 mediating both processes. In addition, NREP expression showed a positive correlation with the abundance of M2 macrophages, which are potent immunosuppressors. Together, these results indicate that NREP is overexpressed in GC and affects GC prognosis. Thus, NREP could be a prognostic biomarker and therapeutic target for GC.
| S-EPMC8565479 | biostudies-literature
Project description:TAFA chemokine like family member 5 (TAFA5), a TAFA family member that encodes small secreted proteins in the central nervous system, has been demonstrated to have increased expression in human malignancies. However, the expression and function of TAFA5 in gastric cancer (GC) remains unclear. In the present study, public datasets and human GC samples were used to determine the TAFA5 expression levels. The results revealed that TAFA5 was upregulated in GC when compared with adjacent normal tissues. Overexpression of TAFA5 in GC was associated with poor differentiation, and worse tumor, nodal and metastasis stages. In addition, high TAFA5 expression was correlated with unfavorable patient prognoses. In vitro experiments indicated that downregulation of TAFA5 inhibited the proliferation and migration of GC cell lines. Finally, the results from gene set enrichment analysis using data from The Cancer Genome Atlas revealed that TAFA5 expression was significantly correlated with genes associated with epithelial?mesenchymal transition, which was further confirmed by western blot analysis. In conclusion, the results of the present study suggested that TAFA5 had significant effects on GC progression, suggesting that it may serve as a potential therapeutic target for GC therapy.
| S-EPMC6797941 | biostudies-literature
Project description:Cullin 4B (CUL4B), a scaffold protein that assembles CRL4B ubiquitin ligase complexes, has been reported to be overexpressed in several types of solid tumors and contributes to epigenetic silencing of tumor suppressor. However, its clinical significance and the molecular mechanisms underlying its regulation in gastric cancer (GC) remain largely unknown. Here, we showed that CUL4B was elevated in GC tissues and its overexpression was positively correlated with poor prognosis and lymph node metastasis. CUL4B knockdown in GC cells decreased proliferation, mesenchymal transition and invasion in vitro, as well as tumor growth and metastasis in nude mice, and CUL4B overexpression induced the opposite results. Further studies showed that miR-101 could inhibit CUL4B expression by directly targeting its 3’-UTR and they were inversely correlated in clinical GC specimens. Notably, a positive relationship between CUL4B and HER2 was found in GC clinical specimens, GC cells and GC xenograft tumors. Through bioinformatics analysis of miRNA-seq data and target prediction, we nominated miR-125a as a direct target of CUL4B. ChIP assays demonstrated that CUL4B directly repressed miR-125a expression by physically binding to its promoter. In addition, we confirmed miR-125a is the target of HER2. Consequently, we demonstrated that CUL4B can up-regulate HER2 expression through repressing miR-125a. Most importantly, silencing of HER2 by Herceptin or siRNA partially reversed CUL4B-induced epithelial-to-mesenchymal transition (EMT), cell invasion and metastasis in vitro and in vivo. These findings define a CUL4B-miR-125a-HER2 regulatory mechanism shed light on CUL4B oncogenic mechanisms and reveals promising therapeutic targets for progressive GC. CUL4B proteins are frequently upregulated in human cancer, yet little is known about the underlying molecular mechanisms of CUL4B induced gastric cancer(GC) carcigenesis.Here, we uncover the critical role of CUL4B in gastric cancer growth and metastasis through the regulation of HER2 expression.CUL4B contributes to GC invasion and metastasis by transcriptional repression of HER2 targeting miR-125a, which provide a new insight into how CUL4B regulates GC progression and metastasis.
2017-11-25 | GSE90501 | GEO
Project description:ChIP-seq of HOXC10 in gastric cancer cell
| PRJNA624322 | ENA