RESUMO
Pancreatic cancer is a common malignancy whose prognosis and treatment of pancreatic cancer is extremely poor, with only 20% of patients reaching two years of survival. Previous findings have shown that the tumor suppressor p53 is involved in the development of various types of cancer, including pancreatic cancer. Additionally, p53 is able to activate TP53INP1 transcription by regulating several phenotypes of cancer cells. Using gain and loss-of-function assays, the aim of the present study was to examine the relationships between miR-19a/b and cancer development as well as potential underlying mechanisms. The results showed that miR-19a/b identified a positive feedback regulation of p53/TP53INP1 axis. Additionally, p53 upregulated the TP53INP1 level in pancreatic cancer cells. However, overexpressed miR-19a/b partially restored the TP53 function in the pancreatic cancer cells while miR-19a/b downregulated TP53INP1 protein by directly targeting 3'UTR of its mRNA at the post-transcriptional level. In addition, the patient tissues identified that the miR-19a/b level in pancreatic cancer tissues was conversely correlated with TP53 and TP53INP1 expression. The results provide evidence for revealing the molecular mechanism involved in the development of pancreatic cancer and may be useful in the identification of new therapeutic targets for pancreatic cancer.
Assuntos
Proteínas de Transporte/genética , Proteínas de Choque Térmico/genética , MicroRNAs/genética , Neoplasias Pancreáticas/metabolismo , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas , Apoptose , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Humanos , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Leukemia seriously threatens human life and health. MicroRNAs can regulate cell growth, proliferation, and death. This article investigated the role of miR-29 on regulating leukemia cell growth, proliferation, and apoptosis. MATERIAL AND METHODS: miR-29 and scramble miRNA were transfected to K562 cells. MTT assay, colony formation assay, caspase-3 activity detection, and flow cytometry were applied to test miR-29 effect on cell growth, proliferation, and apoptosis. Western blot was used to detect Forkhead box protein M1 (FoxM1) protein expression. After we transfected miR-29, K562 cells were transfected with FoxM1 siRNA to test cell apoptosis. RESULTS: K562 cell growth and proliferation were inhibited after transfection with miR-29. Apoptosis phenome and caspase-3 activation were observed. FoxM1 level decreased. SiRNA FoxM1 enhanced miR-29-induced K562 cell apoptosis. FoxM1 overexpression suppressed miR-26-induced K562 cell apoptosis. CONCLUSIONS: MiR-29 restrained K562 cell growth and proliferation. MiR-29 induced K562 cell apoptosis through down-regulating FoxM1.
