Introduction: Patients with Nasopharyngeal carcinoma (NPC) usually diagnosed at advanced cancer stage and re- current case. Rac1 have become an emerging therapeutic target for metastasis cancer. This gene is critically involved in cell polarization and reactive oxygen species-mediated cell killing. This study aims to investigate the Rac1 activ- ities in NPC/HK1 cell line using siRNA approach and evaluate the calcium deposition profile. Methods: The NPC/ HK1cells were transfected with Rac1-siRNA (siRac1) at concentrations of 50nM, 100nM and 200nM for 24 hours and stained with alizarin red s for calcium mineralization profile. Levels of Rac1 gene expression were measured via qRT-PCR followed by the time dependent assessment for 24, 48 and 72 hours. Results: Findings revealed that siRac1 concentrations of 200nM (p-value
Gene manipulation tools have transformed biomedical research and improved the possibilities of their uses for therapeutic purposes. These tools have aided effective genomic modification in many organisms and have been successfully applied in biomedical engineering, biotechnology and biomedicine. They also shown a potential for therapeutic applications to alleviate genetic and non-genetic diseases. Small interfering RNA (siRNA) and clustered regularly inter-spaced short-palindromic repeat/associated-protein system (CRISPR/Cas) are two of the tools applied in genetic manipulation. This review aims to evaluate the molecular influence of siRNA and CRISPR/Cas as novel tools for genetic manipulations. This review discusses the molecular mechanism of siRNA and CRISPR/Cas, and the advantages and disadvantages of siRNA and CRISPR/Cas. This review also presents comparison between siRNA and CRISPR/Cas as potential tools for gene therapy. siRNA therapeutic applications occur through protein knockout with- out causing damage to cells. siRNA knocks down gene expression at the mRNA level, whereas CRISPR/Cas knocks out gene permanently at the DNA level. Inconclusion, gene manipulation tools have potential for applications that improve therapeutic strategies and plant-derived products, but ethical standards must be established before the clin- ical application of gene editing.
Emanuel syndrome, also referred to as supernumerary der(22) or t(11;22) syndrome, is a rare genomic syndrome. Patients are normally presented with multiple congenital anomalies and severe developmental disabilities. Affected newborns usually carry a derivative chromosome 22 inherited from either parent, which stems from a balanced translocation between chromosomes 11 and 22. Unfortunately, identification of Emanuel syndrome carriers is diffi- cult as balanced translocations do not typically present symptoms. We identified two patients diagnosed as Emanuel syndrome with identical chromosomal aberration: 47,XX,+der(22)t(11;22)(q24;q12.1)mat karyotype but presenting variable phenotypic features. Emanuel syndrome patients present variable phenotypes and karyotypes have also been inconsistent albeit the existence of a derivative chromosome 22. Our data suggests that there may exist ac- companying genetic aberrations which influence the outcome of Emanuel syndrome phenotypes but it should be cautioned that more patient observations, diagnostic data and research is required before conclusions can be drawn on definitive karyotypic-phenotypic correlations.
Introduction: Rac1 and STIM1 genes are emerging therapeutic targets for cancers. However, their roles in acute my- eloid leukaemia (AML) are not well understood. The goal of this study was to evaluate the effects of dose and time on Rac1 and STIM1 knockdown in the AML cell line model (THP-1 cells). Methods: THP-1 cells were transfected with siRac1 at doses of 50, 100, and 200 nM or dsiSTIM1 at doses of 2, 5, and 10 nM. Expression level of Rac1 and STIM1 then were assessed at time points between 12 and 72 h post-transfection using real-time reverse transcription poly- merase chain reaction. Results: Compared to the control, 87% Rac1 knockdown was attained with 50 nM siRac1 at 24 h post-transfection, and 70% STIM1 knockdown was achieved with 10 nM dsiSTIM1 at 48 h post-transfection. Conclusion: These results show that effective knockdown of Rac1 and STIM1 is possible, and therapy that includes Rac1 and STIM1 inhibitors eventually could provide a new and highly effective strategy for AML treatment.
The human leukaemia develops with abnormal increase of blast cells in the bone marrow. Leukaemia is caused by genetic aberrations which activates proto-oncogenes and inactivates tumor-suppressor genes and eventually leads to leukemogenesis. Myelodysplastic syndrome is a preleukemic state which shares similar symptoms and causative factors as leukaemia. FOXO3 and c-Myc have been increasingly recognized as key regulatory genes involved in the initiation and development of leukaemia and myelodysplastic syndromes. Their roles in these diseases is being investigated and findings thus far has indicated that FOXO3 acts as a tumor suppressor while c-Myc has been identified as a proto-oncogene. Currently published literature indicate that there are limited research on the correlation between FOXO3 and c-Myc especially in leukaemia and myelodysplastic syndrome. This review will focus on the key regulatory roles of FOXO3 and c-Myc in leukaemia and myelodysplastic syndrome.