Articles written in Journal of Biosciences
Volume 33 Issue 5 December 2008 pp 723-730 Articles
Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour, antifungal, antibacterial, antioxidant and antivenom properties. We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS) isolated from
Volume 37 Issue 2 June 2012 pp 243-257 Articles
Of all the causes identified for the disease hyper-immunoglobulinemia E syndrome (HIES), a homozygous mutation in tyrosine kinase2 (TYK2) and heterozygous mutations in STAT3 are implicated the defects in Jak/STAT signalling pathway in the pathogenesis of HIES. Mutations of STAT3 have been frequently clinically identified in autosomal-dominant (AD) HIES patients’ cells, and therefore, the genotype of STAT3 has been associated with the phenotype of HIES. Here, we conducted studies on the functional loss of the seven specific STAT3 mutations correlated with ADHIES. Using STAT3-null human colon carcinoma cell line A4 cells, we generated seven mutants of STAT3 bearing single mutations clinically identified in AD-HIES patients’ cells and studied the functional loss of these mutants in IL-6-Jak/STAT3 signalling pathway. Our results show that five STAT3 mutants bearing mutations in the DNA-binding domain maintain the phosphorylation of Tyr705 and the ability of dimerization while the other two with mutations in SH2 domain are devoid of the phosphorylation of Try705 and abrogate the dimerization in response to IL-6. The phosphorylation of Ser727 in these mutants shows diversity in response to IL-6. These mutations eventually converge on the abnormalities of the IL-6/Gp130/Jak2-mediated STAT3 transactivation on target genes, indicative of the dysregulation of JAK/STAT signalling present in HIES.
Volume 44 Issue 4 September 2019 Article ID 0102 Review
Prostate cancer (PCa) represents the most frequently diagnosed cancer in men. Cisplatin, also known as cis-diamminedichloroplatinum(DDP), is a standard chemotherapeutic agent used to treat PCa, and DDP resistance remains one important obstacle inDDP-based chemotherapy. In our research, we found miR-425-5p was down-regulated in PCa and even lower in DDP-resistantPCa determined by quantitative polymerase chain reaction; in contrast, GSK3b mRNA expression was upregulated in PCa andeven higher in DDP-resistant PCa. Moreover, there was a modest but significant inverse correlation between the expression ofGSK3bmRNA and miR-425-5p. Functional experiments showed that miR-425-5p mimic inhibited DDP resistance as evidencedby a promoted apoptosis rate (flow cytometry) and suppressed cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay) and expressions of MDR1 andMRP1 (western blotting) in DU145/DDP and PC3/DDP cells. Luciferase reporterassay and RNA immunoprecipitation identifiedGSK3b was a potential target of miR-425-5p. The effect ofmiR-425-5pmimic onDDP resistance was partially reversed by pcDNA-GSK3b. Mechanically, miR-425-5p mimic reduced expression of b-catenin,cyclin D1 and C-myc, which was further blocked when GSK3b overexpressed. In vivo experiments, recovery of GSK3bprevented xenograft tumor growth and DDP resistance in the presence of miR-425-5p mimic. To sum up, miR-425-5p upregulationmight sensitize human PCa to DDP by targeting GSK3b and inactivating the Wnt/b-catenin signaling pathway.
Volume 44 | Issue 6
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