RESUMO
Breast cancer (BC) is one of the most common malignancies occurring in women worldwide, and its incidence is increasing each year. Accumulating evidence indicated that Myosin VI (MYO6) functions as a gene associated with tumor progression in several cancers. However, the potential role of MYO6 and its underlying mechanisms in the development and progression of BC remains unknown. Herein, we examined the expression levels of MYO6 in BC cells and tissues by western blot and immunohistochemistry. Loss- and gain-of-function investigations in vitro were performed to determine the biological functions of MYO6. And in vivo effects of MYO6 on tumorigenesis were investigated in nude mice. Our findings showed that the expression of MYO6 was up-regulated in breast cancer, and its high expression was correlated with poor prognosis. Further investigation exhibited that silencing the expression of MYO6 significantly inhibited cell proliferation, migration and invasion, whereas overexpression of MYO6 enhanced these abilities in vitro. Also, reduced expression of MYO6 significantly retarded the tumor growth in vivo. Mechanistically, Gene Set Enrichment Analysis (GSEA) revealed that MYO6 was involved in mitogen-activated protein kinase (MAPK) pathway. Moreover, we proved that MYO6 enhanced BC proliferation, migration and invasion via increasing the expression of phosphorylated ERK1/2. Taken together, our findings highlight the role of MYO6 in promoting BC cell progression through MAPK/ERK pathway, suggesting it may be a new potential therapeutic and prognostic target for BC patients.
Assuntos
Sistema de Sinalização das MAP Quinases , Proteínas Quinases Ativadas por Mitógeno , Animais , Feminino , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/genética , Transdução de SinaisRESUMO
AIM: To screen the differential expressed genes in colorectal cancer and polyp tissue samples. METHODS: Tissue specimens containing 16 cases of colorectal adenocarcinoma and colorectal polyp vs normal mucosae were collected and subjected to cDNA microarray and bioinformatical analyses. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm some of the cDNA microarray data. RESULTS: The experimental data showed that eight genes were differentially expressed, most of which were upregulated in adenomatous polyp lesions. Forty-six genes expressions were altered in colorectal cancers, of which 29 were upregulated and 17 downregulated, as compared to the normal mucosae. In addition, 18 genes were similarly altered in both adenomatous polyps and colorectal cancer. qRT-PCR analyses confirmed the cDNA microarray data for four of those 18 genes: MTA1, PDCD4, TSC1 and PDGFRA. CONCLUSION: These differentially expressed genes likely represent biomarkers for early detection of colorectal cancer and may be potential therapeutic targets after confirmed by further studies.
Assuntos
Pólipos do Colo/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/patologia , Adulto , Idoso , Biomarcadores , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Adulto JovemRESUMO
AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and the exposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.
