جستجوی مقالات مرتبط با کلیدواژه « ریز rna » در نشریات گروه « پزشکی »

Background and purpose: Lentiviral vectors (LVs) are suitable candidates for gene delivery to cells with stable and high-level of transgene expression in target cells. MicroRNAs (miRNAs, miRs) are non-protein coding, short (~22 nucleotides) and single-stranded RNAs that act as post-transcriptional regulators of gene expression, and are involved in various cellular processes, including proliferation, differentiation and apoptosis. Several studies have shown that miR-499a promotes cardiac differentiation in cardiac stem cells. So, the aim of our study was to construct lentiviruses carrying miRNA-499a. Specific sequences of miRNA-499a (3p and 5p) were designed and constructed. Then, miRNA-499a was cloned into lentiviral vector. Analytical digestion and nucleotide sequence analysis were performed to ensure successful introduction of the miRNA to the vector. Then, the lentiviral particles produced (miRNA-499a-3p and miRNA-499a-5p) were used for transduction of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Analytical digestion and sequence analysis confirmed the accuracy of the constructs. The high expression of eGFP represented the high efficiency of transfection and transduction. The lentiviral particles carrying miRNA-499a-3p/5p were made and could transduce hBM-MSCs. In this study we made lentiviral particles carrying miR-499a that could be used for differentiation of stem cells to cardiomyocytes.

Pancreatic cancer is one the most malignant cancers in human. A great percentage of patients die annually due to lack of early detection as well as efficient treatment strategies. Only five-year survival rate is still only seen in 5% of patients. Major problem of this deadly disease is the intrinsic and acquired resistance to current chemotherapeutic agents such as gemcitabine. So far, different molecular mechanisms are attributed to gemcitabine resistance. For instance, genetic mechanisms, aberrant gene expression in cellular signaling pathways, cancer stem cells, impaired apoptosis related genes, epigenetic changes and potential role of microRNAs have been identified in gemcitabine resistance of pancreatic cancer. Improving the drug efficacy and overcoming to drug resistance is the current goal in treatment of pancreatic cancer. Understanding the cellular and molecular mechanisms of resistance can help us to develop novel therapeutic approaches leading to increased effectiveness of current treatments. In this review, we summarized the molecular mechanisms involved in gemcitabine resistance in pancreatic cancer.

MicroRNAs are small non-coding regulatory molecules that are involved in diverse biological processes such as proliferation, differentiation and apoptosis. Down regulation of miR-29b1 has been found in some of cancers that indicate important roles of this molecule in histological development and cancer. Whereas induction of apoptosis in cancer cells is important for their therapy, in this study, our goal was to examine the effect of miR-29b1 over-expression on apoptosis using the lentiviral structure in HL60 cell line. Permanent overexpression of miR-29b1 was established using a lentiviral vector construct containing the precursor of miR-29b1 sequence. Then, HL60 cells treated by miR-29b1 lentivirus. 48 and 72 hours after transduction, cell proliferation inhibition was estimated by MTT assay. Detection of apoptotic cells was evaluated by EtBr/AO double staining technique and flow cytometry using Annexin V and Caspase-3 activity was measured by caspase-3 colorimetric activity assay. Data analysis was done with SPSS 13 softwer and t-test. According to our results, overexpression of miR-29b1 led to increase apoptosis. As apoptosis in the test group compared with the control group showed about 3-fold increase. Data analysis showed a significant increase compared to the control group (P<0.05). According to findings of present study, miR-29b1 can induce apoptosis in HL60 cell line. Apoptosis stimulation by miRNAs is probably one of the best and applicable ways to induce death in cancer cells. These data support a tumor suppressor role of miR-29b1, synthetic miR-29b1 might be used as a novel epigenetic therapy in future.