Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines. In this study, we evaluated the contribution of these proteins to the response of drug sensitive cells. Depletion of UBE2L6 or ISG15 with siRNA did not influence caspase-3 activation or nuclear fragmentation following treatment with 5-fluorouracil (5-FU). We assessed autophagy by analysis of LC3II expression and Cyto-ID staining. Depletion of either ISG15 or UBE2L6 resulted in enhanced endogenous autophagic flux. An increase in autophagic flux was also observed following treatment with cytotoxic drugs (5-FU, rapamycin). In ISG15 depleted cells, this increase in autophagy was associated with improved recovery of drug treated cells. In contrast, UBE2L6 depleted cells, did not show enhanced recovery. UBE2L6 may therefore influence additional targets that limit the pro-survival effect of ISG15 depletion. These data identify UBE2L6 and ISG15 as novel inhibitors of autophagy, with the potential to influence chemosensitivity in esophageal cancer cells.
 ...
PMID:UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells. 3201 Apr 32

As a typical product in the Miallard reaction, research on the quantitative detection of furosine is abundant, while its bioactivities and toxic effects are still unclear. Our own work recently demonstrated the induction of furosine on apoptosis in HepG2 cells, while the related mechanism remained elusive. In this study, the effects of furosine on cell viability and apoptosis were detected to select the proper dosage, and transcriptomics detection and data analysis were performed to screen out the special genes. Additionally, SiRNA fragments of the selected genes were designed and transfected into HepG2 cells to validate the role of these genes in inducing apoptosis. Results showed that furosine inhibited cell viability and induced cell apoptosis in a dose-dependent manner, as well as activated expressions of the selected genes STAT1 (signal transducer and activator of transcription 1), STAT2 (signal transducer and activator of transcription 2), UBA7 (ubiquitin-like modifier activating enzyme 7), and UBE2L6 (ubiquitin-conjugating enzyme E2L6), which significantly affected downstream apoptosis factors Caspase-3 (cysteinyl aspartate specific proteinase-3), Bcl-2 (B-cell lymphoma gene-2), Bax (BCL2-Associated gene X), and Caspase-9 (cysteinyl aspartate specific proteinase-9). For the first time, we revealed furosine induced apoptosis through two transcriptional regulators (STAT1 and STAT2) and two ubiquitination-related enzymes (UBA7 and UBE2L6).
 ...
PMID:Furosine Induced Apoptosis by the Regulation of STAT1/STAT2 and UBA7/UBE2L6 Genes in HepG2 Cells. 2985 9