RESUMO
OBJECTIVE: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Chemotherapy resistance is a considerable obstacle to CRC treatment. Circular RNAs (circRNAs) are involved in the pathogenesis of many cancers. This study aimed to investigate the role and molecular basis of DEAD-box helicase 17 circRNA (circDDX17) in 5-fluorouracil (5-Fu) sensitivity and CRC progression. MATERIALS AND METHODS: The levels of circDDX17, microRNA-31-5p (miR-31-5p) and kidney ankyrin repeat-containing protein 1 (KANK1) were detected by quantitative real-time PCR or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis rate was monitored by flow cytometry. Cell invasion capacity was evaluated by transwell assay. Western blot assay was conducted to measure the expression of matrix metallopeptidase 9 (MMP9) and E-cadherin. The interaction among circDDX17, miR-31-5p and KANK1 was indicated by bioinformatics analysis and dual-luciferase reporter assay. Xenograft assay was performed to analyze tumor growth and 5-Fu sensitivity in vivo. RESULTS: CircDDX17 and KANK1 were down-regulated, while miR-31-5p was upregulated in CRC tissues and cells. Upregulation of circDDX17 enhanced 5-Fu sensitivity and impeded CRC development. CircDDX17 inhibited 5-Fu resistance and CRC progression via sponging miR-31-5p. Besides, KANK1 depletion attenuated the effect of circDDX17 upregulation on chemosensitivity and CRC progression. CircDDX17 regulated KANK1 expression by binding to miR-31-5p. Moreover, circDDX17 overexpression blocked tumor growth and elevated 5-Fu sensitivity in vivo. CONCLUSIONS: Upregulation of circDDX17 strengthened chemosensitivity of CRC to 5-Fu and blocked CRC progression by regulating miR-31-5p/KANK1 axis, which might provide an effective treatment strategy for CRC patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Neoplasias Colorretais/genética , Proteínas do Citoesqueleto/genética , RNA Helicases DEAD-box/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , RNA Circular/genética , Animais , Antimetabólitos Antineoplásicos , Linhagem Celular , Neoplasias Colorretais/patologia , Fluoruracila , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carga TumoralRESUMO
Eighteen patients with leukemia have received HLA-identical allogeneic bone marrow transplantation (BMT) at our hospital since 1981. Fifteen of these patients have been living without relapse. for prophylaxis of GVHD, MTX was used in 8 patients, and cyclosporine (CSP) together with MTX in 6 patients, 3 received multiple agents at much smaller dosage, including monoclonal antibody. All patients received intravenous placental gamma-globulin, and 16 received garlic extract. Three patients died. One, who neither received MTX, nor CSP died of hyperacute GVHD, one who did not receive garlic extract died of GMV pneumonia, and the third one died of tuberculosis 18 months after BMT.
Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Transplante HomólogoRESUMO
The effect of harringtonine (HA) in various concentrations on HL-60 was evaluated. 0.10 microgram/ml HA showed a strong cell killing effect, and 0.025 microgram/ml HA a weak differentiation induction accompanied by cell growth retardation. Differentiation induction did not occur in 5 other human leukemic cell lines. We consider that antileukemic effect of HA is cytotoxicity, not differentiation induction.
