Project description:Cytarabine is the main drug for acute myeloid leukemia (AML) treatment; however, drug resistance hinders the treatment of AML. Although microRNA (miRNA) alteration is one of the well-recognized mechanisms underlying drug resistance in AML, few studies have investigated the role and function of miRNAs in the development of cytarabine resistance. In this study, total RNA was isolated from parental HL60 and cytarabine resistant HL60 (R-HL60) cells. Subsequently, miRNAs and mRNAs were detected using small RNA sequencing and gene expression array, respectively. The miRNAs and genes with ≥ 2-fold difference in expression between HL60 and R-HL60 cells were screened out. Negatively correlated miRNA–mRNA pairs were selected as candidate miRNA–mRNA target pairs by using the miRDB, Targetscan or miRTar databases. Functional enrichment analysis of differentially expressed genes (DEGs) included in the candidate miRNA–mRNA network was performed. The results revealed that CCL2, SOX9, SLC8A1, ICAM1, CXCL10, SIPR2, FGFR1, OVOL2, MITF, and CARD10 were simultaneously involved in seven GO pathways, namely the regulation of cell migration, regulation of locomotion, regulation of cellular component movement, cell migration, locomotion, cell motility, localization of cell. These genes were negatively correlated with the altered miRNAs (miR-1-3p, miR-155-5p, miR-1255b-5p, miR-200c-5p, miR-3609, miR-1285-3p, miR-124-3p, miR-146a-5p, miR-497a-5p, and miR-3150a-5p), suggesting that they are the potential targets of the miRNAs to regulate cell migration behavior or ability. Therefore, our results advance our understanding of the regulatory mechanism underlying cytarabine resistance development, specifically related to miRNAs.
Project description:Cytarabine is the main drug for acute myeloid leukemia (AML) treatment; however, drug resistance hinders the treatment of AML. Although microRNA (miRNA) alteration is one of the well-recognized mechanisms underlying drug resistance in AML, few studies have investigated the role and function of miRNAs in the development of cytarabine resistance. In this study, total RNA was isolated from parental HL60 and cytarabine resistant HL60 (R-HL60) cells. Subsequently, miRNAs and mRNAs were detected using small RNA sequencing and gene expression array, respectively. The miRNAs and genes with ≥ 2-fold difference in expression between HL60 and R-HL60 cells were screened out. Negatively correlated miRNA–mRNA pairs were selected as candidate miRNA–mRNA target pairs by using the miRDB, Targetscan or miRTar databases. Functional enrichment analysis of differentially expressed genes (DEGs) included in the candidate miRNA–mRNA network was performed. The results revealed that CCL2, SOX9, SLC8A1, ICAM1, CXCL10, SIPR2, FGFR1, OVOL2, MITF, and CARD10 were simultaneously involved in seven GO pathways, namely the regulation of cell migration, regulation of locomotion, regulation of cellular component movement, cell migration, locomotion, cell motility, localization of cell. These genes were negatively correlated with the altered miRNAs (miR-1-3p, miR-155-5p, miR-1255b-5p, miR-200c-5p, miR-3609, miR-1285-3p, miR-124-3p, miR-146a-5p, miR-497a-5p, and miR-3150a-5p), suggesting that they are the potential targets of the miRNAs to regulate cell migration behavior or ability. Therefore, our results advance our understanding of the regulatory mechanism underlying cytarabine resistance development, specifically related to miRNAs.
Project description:Radiation-resistant of acute myeloid leukemia cell present challenges to treatment, and the acquisition of resistance to ionizing radiation (IR) is a matter of clinical concern. However, little information is available on the behavior of radio-resistant leukemia in terms of gene expression profiles and intercellular communication. In this study, mRNA microarray was used to analyze the intracellular genetic network in the established radio-resistant HL60 (Res-HL60) cell line. Significant changes in the expression of 7,309 known mRNAs were observed in Res-HL60 relative to control. In addition, 7 mRNAs were determined as targets because significant changes in the expression were observed using Ingenuity analysis software, confirming the quantitative RT-PCR. However, extracellular vesicles from Res-HL60 cells did not include these target mRNAs. These results suggest that radio-resistant leukemia model is regulated by the expression and suppression of specific mRNAs, and these molecules are not transferred between cells by extracellular vesicles.
Project description:Human Promyelocytic Leukemia Cell Line HL60 has been used extensively as a model for myeloid differentiation and leukemia. HL60-RG cell is its sub-line and shows a higher growth rate. In this study, we carried out a genome scan using SNP 10k mapping array on both cells. Comparative study on chromosomal changes of these cells will give us information on mechanism of tumor progression. Keywords: cell type comparison