RESUMO
MicroRNA-149* (miRNA-149*) functions as an oncogenic regulator in human melanoma. However, the effect of miRNA-149* on T-cell acute lymphoblastic leukemia (T-ALL) is unclear. Here we aimed to analyze the effects of miRNA-149* on in vitro T-ALL cells and to uncover the target for miRNA-149* in these cells. The miRNA-149* level was determined in multiple cell lines and bone marrow cells derived from patients with T-ALL, B acute lymphoblastic leukemia (B-ALL), acute myelocytic leukemia (AML), and healthy donors. We found that miRNA-149* was highly expressed in T-ALL cell lines and T-ALL patients' bone marrow samples. JunB was identified as a direct target of miR-149*. miRNA-149* mimics downregulated JunB levels in Molt-4 and Jurkat cells, while miRNA-149* inhibitors dramatically upregulated JunB expression in these cells. miRNA-149* mimics promoted proliferation, decreased the proportion of cells in G1 phase, and reduced cell apoptosis in T-ALL cells, while miRNA-149* inhibitors prevented these effects. miRNA-149* mimics downregulated p21 and upregulated cyclinD1, 4EBP1, and p70s6k in Molt-4 and Jurkat cells. Again, inhibitors prevented these effects. Our findings demonstrate that miRNA-149* may serve as an oncogenic regulator in T-ALL by negatively regulating JunB.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Fatores de Transcrição/genética , Apoptose/genética , Apoptose/imunologia , Western Blotting , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , MicroRNAs/imunologia , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/imunologiaRESUMO
BACKGROUND: The aim of this study was to investigate differences of miRNA-34a expression in benign and malignant colorectal lesions. MATERIALS AND METHODS: Samples of cancer, paraneoplastic tissues and polyps were selected and total RNA was extracted by conventional methods for real-time PCR to detect the miRNA- 34a expression. In addition, the LOVO colorectal cancer cell line was cultured, treated with the demethylating agent 5-azacytidine and screened for differentially expressed miRNA-34a. RESULTS: After the drug treatment, the miRNA-34a expression of colorectal cancer cell line LOVO was increased and real-time PCR showed that levels of expression in both cell line and colorectal cancer tissues were low, as compared to paraneoplastic tissue (p<0.05). Polyps tissues had significantly higher expression than paraneoplastic and colorectal cancer samples (p<0.05). CONCLUSIONS: miRNA-34a-5p may play a role as a tumor suppressor gene in colorectal cancer, with involvement of DNA methylation.
Assuntos
Adenocarcinoma/genética , Adenoma/genética , Pólipos do Colo/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Adenocarcinoma/química , Adenoma/química , Idoso , Linhagem Celular Tumoral , Colo/química , Pólipos do Colo/química , Neoplasias Colorretais/química , Neoplasias Colorretais/patologia , Metilação de DNA , Feminino , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , RNA Mensageiro/análise , Reto/químicaRESUMO
OBJECTIVE: To explore the molecular mechanism and prevention of retinoic acid syndrome (RAS). METHODS: SDF-1 alpha mRNA from healthy adult lung tissue was measured by RT-PCR, CXCR4 protein expression on the cell membrane of APL cells induced by ATRA (APL-ATRA) was tested by FCM, and the rotary cell culture system (RCCS) was used to build a modal for in vitro stimulation of APL-ATRA infiltrating human lung tissue. The ability of APL-ATRA in adhesion, migration and infiltration was observed by interference from DEX, Ara-C and DNR. RESULTS: The APL-ATRA cells could evidently infiltrate into normal lung tissue. Mean fluorescence intensity (MFI) of CXCR4 on the cell membrane of APL-ATRA cells was 30.6 +/- 1.8, which was much higher than that on unspecialized APL cells (9.8 +/- 4.2). SDF-1 alpha mRNA expression was detected positive in all 6 lung tissue. Contrary to the control groups, DEX could dramatically restrain the ability of APL-ATRA cells in adhesion and migration [(27.2 +/- 2.6)% vs. (46.0 +/- 3.0)%, (28.1 +/- 4.0)% vs. (48.2 +/- 3.0)%], while Ara-C and DNR could distinctly depress the ability in adhesion, migration and infiltration [(28.1 +/- 3.0)%, (30.2 +/- 3.2)% vs. (46.0 +/- 3.0)%; (29.0 +/- 4.0)%, (23.0 +/- 5.2)% vs. (48.2 +/- 3.0)%; (16.8 +/- 7.6)%, (17.1 +/- 6.0)% vs. (43.6 +/- 5.0)%]. CONCLUSION: In vitro APL-ATRA cells can infiltrate into the human lung tissue. High expression of CXCR4 on APL-ATRA and SDF-1 alpha in the lung tissue may be one of the molecular mechanisms of the lung infiltration and RAS. DEX, Ara-C and DNR can dramatically restrain the ability of APL-ATRA cells in adhesion, migration and infiltration.
Assuntos
Quimiocina CXCL12/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Receptores CXCR4/metabolismo , Tretinoína/efeitos adversos , Adolescente , Adulto , Adesão Celular , Técnicas de Cultura de Células , Movimento Celular , Quimiocina CXCL12/genética , Criança , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Receptores CXCR4/genética , Células Tumorais CultivadasRESUMO
OBJECTIVE: To study the main side effects of As(2)O(3) and the way of prevention. METHODS: The changes of body weight and various systems of body were observed after treatment with As(2)O(3) injection. The arsenic content in blood, urine and hair was detected with atom absorbed-spectrum analysis. RESULTS: Mild reactions were observed in 57.43% (147/256) of the patients and they could subside after cessation of arsenic treatment or allotherapy. Chronic mild poisoning manifestations including arsenic furuncle, liver dysfunction and peripheral nerve injury were found in 2.73% (7/256) of the patients and they subsided gradually after treatment. Chronic severe poisoning was found in 1.17% of the patients and all of them died of liver failure. As(2)O(3) might cause decrease of peripheral blood WBC in catabatic patients. There was no infection after allopathy without ceasing arsenic medication. The results showed that As(2)O(3) could distribute over and discharge from the plasma without accumulation in blood. The results also demonstrated the main route of excretion for As(2)O(3) is through urine and there is definite accumulation in the hair 50 days after treatment. CONCLUSION: Most of the side effects of As(2)O(3) are mild and recoverable. Allotherapy could be effective to relieve the complications without stopping arsenic medication. A few patients with complicating hepatitis may suffer from chronic poisoning. As(2)O(3) may cause increase of peripheral blood WBC in induced catabatic APL patients. The side effects must be prevented early.