DJ-1 Alters Epirubicin-induced Apoptosis via Modulating Epirubicin-activated Autophagy in Human Gastric Cancer Cells

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 D J-1 may be a chemoresistance-related gene.But the association between D J-1 and drug resistance of epirubicin in gastric cancer is still ambiguous.In the present report,we explored whether and how D J-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 epirubicin-activated 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.

Expression of Stanniocalcin 2 in Breast Cancer and Its Clinical Sigmiicance

This study aims to explore the expression of stanniocalcin 2(STC2)gene in breast cancer and its clinical significance.Female patients with breast cancer from Zhongnan Hospital of Wuhan University admitted during March 2014 to October 2014 were enrolled in this study.All the tissues used in this experiment included 50 cases of breast cancer tissues and corresponding 50 cases of paracancer normal breast tissues with complete patients'information.The real-time quantitative polymerase chain reaction(qPCR)was applied to detect the expression of STC2 gene in 50 cases of breast cancer and paracancer normal breast tissues.The results showed that the expression level of STC2 gene in 50 cases of breast cancer tissues was significantly higher than that in paracancer normal breast tissues(P<0.001).The expression of STC2 gene was correlated with lymph node metastasis,distant metastasis,TNM stage and histological grade(P<0.001).The expression level of STC2 gene was significantly higher in breast cancer tissues with higher expression of Ki-67(P<0.001).The expression level of STC2 gene was significantly higher in estrogen receptor(ER)positive breast cancer tissues than in ER negative ones(P<0.001).However,different groups of age,pathological type,tumor size,PR expression and human epidermal growth factor receptor-2(HER2)expression did not show significant differences in STC2 expression(P>0.05).In conclusion,the abnormal overexpression of STC2 gene may play a role in the development and progression of breast cancer,and it can be used as an independent metastasis and prognostic factor of breast cancer.In addition,STC2 gene probably promotes the development and metastasis of breast cancer by interacting with estrogen and ER,and it may become a new direction for breast cancer endocrine therapy.

Bioinformatics Analysis and Identification of Potential Genes Associated with Pathogenesis and Prognosis of Gastric Cancer

Objective Gastric cancer(GC)is a deadly cancer and a challenging public health problem globally.This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer.Methods This work selected the overlapping differentially expressed genes(DEGs)in GC from four datasets,the GSE29272,GSE29998,GSE54129 and GSE118916 Gene Expression Omnibus databases.These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched,the relative expression levels and immune infiltrates,the prognostic characteristics and the interaction network.Results In total,55 DEGs increased while 98 decreased in their expression levels.For those DEGs with increased expression,they were mostly concentrated on“focal adhesion”and“ECM-receptor interaction”,whereas DEGs with decreased expression were mostly associated with“gastric acid secretion”and“drug metabolism cytochrome P450”.MCODE and ClueGO results were then integrated to screen 10 hub genes,which were FN1,COL1A1,COL3A1,BGN,TIMP1,COL1A2,LUM,VCAN,COL5A2 and SPP1.Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients.TIMP1 was most significantly related to neutrophils,CD8+T cells,as well as dendritic cells,while LUM was most significantly related to macrophages.Conclusion Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.

Identification of Prognostic Genes for Colon Cancer through Gene Coexpression Network Analysis

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.

Metabolomics study of biochemical changes in the serum and articular synovium tissue of moxibustion in rats with collagen-induced arthritis

Objective:To demonstrate the rheumatoid arthritis(RA)mechanisms by determining the biochemical changes.To investigate the therapeutic mechanism of moxibustion in RA-model rats using a gas chromatography-mass spectrometry(GC-MS)metabolomics approach.Methods:A total of 24 rats were divided into three groups as follows:normal control group,model group and moxibustion group.Rats in model group and moxibustion group were set up collagen-induced arthritis(CIA)model.Rats in moxibustion group were treated by moxibustion.After 3 weeks of intervention,right ankle joint,serum and articular synovium samples were collected.Right ankle joint samples were used for histopathological evaluation between 3 groups to get the pathological changes of tissues and cells.Serum and articular synovium samples were used to analyze the changed metabolites of moxibustion on RA rats by the GC-MS based metabolomics.Results:Treatment of moxibustion not only significantly increased the weight of CIA rats,reduced the swelling of hind paw,arthritic scores,IL-1β,TNF-αbut also improved histopathological evaluation in right ankle joint samples.Sixteen significantly altered metabolites were found in RA rats as potential biomarkers of arthritis.Thirteen metabolites,significantly adjusted by moxibustion to help relieve arthritis,were selected out as biomarkers of antiarthritic mechanism of moxibustion,which were mainly involved in phenylalanine,tyrosine and tryptophan biosynthesis,glycine,serine and threonine metabolism,phenylalanine metabolism,alanine,aspartate and glutamate metabolism,glyoxylate and dicarboxylate metabolism and aminoacyl-tRNA biosynthesis.Conclusions:We have indicated moxibustion treatment is able to resist inflammation in CIA rats effectively.Using GC-MS metabolomics technique,we detect novel metabolites in the moxibustion antiarthritic process,which may aid in advanced understanding of arthritis and therapeutic mechanism of moxibustion.