RESUMO
Long non-coding RNAs are known as key regulators in the progression and metastasis of breast cancer. MIAT originally has been considered as an lncRNA to be associated with a susceptibility to myocardial infarction. Here, we have detected the expression of MIAT in different cancer cells and a series of breast tumor tissue. MIAT expression was much higher in high-grade tumors compared to low-grade ones. Unlike P53 positive tumors, MIAT expression was upregulated in ER, PR, Her2 positive tumor tissues. Knockdown MIAT suppressed breast cancer cell proliferation and caused G1 arrest in cell cycle. Furthermore, downregulation of MIAT promoted apoptosis and significantly decreased migration of breast cancer cells. An increase in the expression of mir-302, mir-150, and a decrease in the expression of mir-29c were detected following MIAT silencing. More importantly, knockdown MIAT significantly elevated the expression of p16Ink4A and Cox2, which commitment cellular senescence in breast cancer cells. Altogether, our results suggest that MIAT involved in breast cancer progression and could be candidate as a novel tumor marker for diagnosis and treatment of breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Senescência Celular , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Feminino , Humanos , Células MCF-7 , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genéticaRESUMO
The octamer-binding transcription factor 4 (OCT4) is involved in regulating pluripotency and self-renewal maintenance of embryonic stem cells. Recently, misexpression of OCT4 has been also reported in some adult stem as well as cancer cells; a finding which is still controversial. In addition to the previously described spliced variants of the gene (e.g., OCT4A and OCT4B), we have recently identified a novel variant of the gene, designated as OCT4-B1. In this study, we investigated a potential expression and function of OCT4B1 in a series of gastric cancer tissues and a gastric adenocarcinoma cell line, AGS. Using the Taqman real-time PCR approach, we have detected the expression of OCT4B1 in tumors with no or much lower expression in marginal samples of the same patients (p < 0.002). We have also analyzed the effects of OCT4B1 knock-down in AGS cell line treated with specific siRNA directed toward OCT4B1. Our data revealed that interfering with the expression of OCT4B1 caused profound changes in the morphology and cell cycle distribution of the cells. Furthermore, down-regulation of OCT4B1 significantly elevated the relative activity of caspase-3/caspase-7 and the rate of apoptosis in the cells (more than 30%). All together, our findings suggest that OCT4B1 has a potential role in tumorigenesis of gastric cancer and candidates the variant as a new tumor marker with potential value in diagnosis and treatment of gastric cancer.
