ABSTRACT
OBJECTIVE: The present study was aimed to identify novel key genes, prognostic biomarkers and molecular pathways implicated in tumorigenesis of colon cancer. METHODS: The microarray data GSE41328 containing 10 colon cancer samples and 10 adjacent normal tissues was analyzed to identify 4763 differentially expressed genes. Meanwhile, another microarray data GSE17536 was performed for weighted gene co-expression network analysis (WGCNA). RESULTS: In present study, 12 co-expressed gene modules associated with tumor progression were identified for further studies. The red module showed the highest association with pathological stage by Pearson's correlation analysis. Functional enrichment analysis revealed that genes in red module focused on cell division, cell proliferation, cell cycle and metabolic related pathway. Then, a total of 26 key hub genes were identified, and GEPIA database was subsequently selected for validation. Holliday junction-recognizing protein (HJURP) and cell division cycle 25 homolog C (CDC25C) were identified as effective prognosis biomarkers, which were all detrimental to prognosis. Gene set enrichment analyses (GSEA) found the two hub genes were enriched in "oocyte meiosis", "oocyte maturation that are progesterone-mediated", "p53 signaling pathway", and "cell cycle". Furthermore, the immunohistochemistry and western blotting showed that HJURP was highly expressed in colon cancer tissue. CONCLUSION: HJURP was identified as a key gene associated with colon cancer progression and prognosis by WGCNA, which might influence the prognosis by regulating cell cycle pathways.
Subject(s)
Biomarkers, Tumor/genetics , Colonic Neoplasms/genetics , DNA-Binding Proteins/genetics , Gene Expression Profiling/methods , cdc25 Phosphatases/genetics , Case-Control Studies , Computational Biology , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , Oligonucleotide Array Sequence Analysis , Prognosis , Signal TransductionABSTRACT
Epirubicin, which is a conventional chemotherapeutic drug for gastric cancer, has innate and adaptive chemoresistance. Recent studies revealed that epirubicin could induce autophagy as a defensive mechanism in drug resistance of mammary carcinoma. Another study implied that DJ-1 may be a chemoresistance-related gene. But the association between DJ-1 and drug resistance of epirubicin in gastric cancer is still ambiguous. In the present report, we explored whether and how DJ-1 conduced to epirubicin-induced apoptosis in gastric cancer. Epirubicin dose-dependently increased the expression of DJ-1 and induced autophagy. Knockdown of DJ-1 notably enhanced epirubicin-induced cell apoptosis, whereas overexpression of DJ-1 attenuated epirubicin-induced cell apoptosis. Further studies revealed that down-regulation of DJ-1 modulated epirubicinactivated autophagy which augmented epirubicin-induced apoptosis. In conclusion, our results validated that DJ-1 reduced epirubicin-induced apoptosis in gastric cancer cells via modulating epirubicin-activated autophagy.
