ABSTRACT
@#Introduction: Cancer is one of the main causes of mortality globally and the incidence has been rising over the years. Studies have shown that miRNAs have the potential as cancer biomarkers. The miR-130a has been reported to be upregulated in several types of cancer, which indicate the important roles of miR-130a in cancer development and metastasis. The aim of this study is to identify potential target genes and to predict the regulatory function of miR130a-3p and 5p in cancer. Methods: Three bioinformatics platforms namely miRWalk, the Database for annotations, visualization and integrated discovery (DAVID) Gene Functional Classification Tool and miRanda-miRSVR analysis tools were used to identify possible interaction between miR-130a and its target. Protein-protein interaction (PPI) network for the predicted target genes was then constructed. Results: The analyses have identified nine predicted target genes for miR-130a-3p (RAPGEF4, SOS2, NRP1, RPS6KB1, MET, IL15, ACVR1, RYR2 and ITPR1), and ten for miR-130a-5p (BCL11A, SPOPL, NLK, PPARGC1A, POU4F2, CPEB4, ST18, RSBN1L, ELF5 and ARID4B), that might play an important role in the development of cancer. Findings from this report suggest that miR-130a may involves in controlling cancer related genes; MET, ACVR1 and BCL11A. miR-130a-3p may regulates MET which involves in apoptosis and metastasis, and ACVR1 which involves in metastasis and angiogenesis. miR-130a-5p may regulates BCL11A which involves in apoptosis, proliferation and tumorigenesis. Conclusion: This study has highlighted the molecular interaction of miR-130a with associated genes and pathways, suggesting therapeutic potential of miR130a as personalised targeted therapy for cancer.
ABSTRACT
Abstract@#Introduction: The alkaloids present in Catharanthus roseus (C. roseus), vinblastine and vincristine are important anticancer agents that cause cell cycle arrest and apoptosis in various types of cell lines. However, there is no previous reports that emphasized the clear mechanisms of anticancer exerted by a crude aquoeus extract of C. roseus although it has been historically used to treat various diseases. Methods: The cytotoxicity effects of C. roseus aqueous extract on Jurkat cells were evaluated by annexin/PI staining, caspase 3/7 assay, JC-1 assay and cell cycle assay. Gene expression profiling was performed by using SmartChip Real-Time PCR system to evaluate the expression profiles of oncology-related genes of Jurkat cells treated with C. roseus aqueous extract. Results: Flow cytometry analysis revealed that the extract has caused S-phase arrest and associated with apoptosis through the externalization of phosphatidylserine and depletion of mitochondrial membrane potential in time-dependent manner. The apoptosis mechanism was mediated through the activation of caspase 3/7. From the gene expression analysis, 8 differentially regulated genes were associated with apoptosis which were CDKN1C, CHI3L2, BIRC8, GFER, ID3-1, BBC3-2, TRAF4 and VCAN. Meanwhile, 7 differentially regulated genes were associated with cell cycle progression which were PIMI-1, CDKN1C, SKP1A, CDC25C, LTBP1, CCNG2 and RBL1. Conclusion: The recent data may facilitate the identification of specific targeting pathways induced by the extract. The information obtained may be used as diagnostic tools, prognostic markers, and predictors of response to C. roseus treatment especially for this particular type of cancer.