Many studies have demonstrated the protective effect of ergothioneine (EGT), the unique sulfur-containing antioxidant in mushrooms, on several aging-related diseases. Nevertheless, to date, no single study has explored the potential...
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality worldwide. Transcription factors (TFs) are crucial proteins that regulate gene expression during cancer progression; however, the roles of TFs in HCC relapse remain unclear. To identify the TFs that drive HCC relapse, the present study constructed co-expression network and identified the Tan module the most relevant to HCC relapse. Numerous hub TFs (highly connected) were subsequently obtained from the Tan module according to the intra-module connectivity and the protein-protein interaction network connectivity. Next, E1A-binding protein p400 (EP400) and TIA1 cytotoxic granule associated RNA binding protein (TIA1) were identified as hub TFs differentially connected between the relapsed and non-relapsed subnetworks. In addition, zinc finger protein 143 (ZNF143) and Yin Yang 1 (YY1) were also identified by using the plugin iRegulon in Cytoscape as master upstream regulatory elements, which could potentially regulate expression of the genes and TFs of the Tan module, respectively. The Kaplan-Meier (KM) curves obtained from KMplot and Gene Expression Profiling Interactive Analysis tools confirmed that the high expression of EP400 and TIA1 were significantly associated with shorter relapse-free survival and disease-free survival of patients with HCC. Furthermore, the KM curves from the UALCAN database demonstrated that high EP400 expression significantly reduced the overall survival of patients with HCC. EP400 and TIA1 may therefore serve as potential prognostic and therapeutic biomarkers.
Abstract. To identify novel hypermethylated genes in colorectal cancer (CRC) and to test their potential application in CRC early diagnosis, a genome-wide screening of 57,723 CpG dinucleotides covering 4,010 genes was performed using MIRA-based microarrays in paired DNA samples extracted from 3 fresh frozen CRC tissues and their matching non-cancer tissues from 3 CRC patients undergoing curative surgery. Candidate hypermethylated genes screened by MIRA-based microarrays were further validated in independent CRC samples. A total of 297 CpG dinucleotides covering 211 genes were found to be hypermethylated in CRC tissues. From these 211 candidate methylated genes, three novel hypermethylated genes with more than four probes positive were picked up for validation. Direct bisulfite sequencing revealed that methylations occurred at multiple CpG sites of these three genes in cancer tissues, especially for PHOX2B and FGF12. Combined bisulfite restriction analysis showed that these three genes were methylated in cancer samples but not in non-cancer samples. We also compared the methylation levels of these three novel hypermethylated genes with those of vimentin and SEPT9, well-known hypermethylated genes in CRC, and found that methylated PHOX2B, FGF12 and GAD2 were better than methylated vimentin and SEPT9 in differentiating CRC cancer tissue from non-cancer tissue. Significant enrichment analysis of GO terms of the hypermethylated genes showed that a high proportion of hypermethylated genes in cancer tissues are involved in the regulation of transcription.In conclusion, we found a set of novel hypermethylated genes in CRC, which may have potential to be used as biomarkers for the early diagnosis of CRC.
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