RESUMO
MicroRNAs (miRNA/miRs) have been demonstrated to be critical posttranscriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR145 was decreased in EOC tissues and cell lines. Overexpression of miR145 inhibited the proliferation, migration and invasion of EOC cells. The Dtype cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR145. Collectively, the results indicated that miR145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR145 was suggested to be a potential miRNAbased therapeutic target in ovarian cancer.
Assuntos
Ciclina D2/genética , Fator de Transcrição E2F3/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Interferência de RNA , Regiões 3' não Traduzidas , Adulto , Idoso , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Genes Reporter , Humanos , Pessoa de Meia-IdadeRESUMO
Endotoxin tolerance is an immunohomeostatic reaction to reiterant lipopolysaccharide (LPS) exposure that maintains a state of altered responsiveness in immune cells, resulting in the inhibition of the pro-inflammatory response and the resolution of inflammation. Microglia constitutes the first line of defense against endogenous and external challenges in the brain. MicroRNAs (miRs) serve a critical function in the regulation of inflammation. The aim of the present study was to investigate whether miR-155 regulates endotoxin tolerance. miR-155 and suppressor of cytokine signaling-1 (SOCS1) mRNA expression was measured using RT-qPCR. The expression of SOCS1 was measured by western blotting and immunofluorescence. TNF-α levels were detected by an enzyme-linked immunosorbent assay. The results indicated that miR-155 expression was significantly downregulated in the microglia and cortex tissue following the induction of endotoxin tolerance. This was consistent with an increase in the expression of SOCS1, a predicted target of miR-155 and key inhibitor of the inflammatory reaction. Transfection with miR-155 inhibitor significantly enhanced SOCS1 expression in the microglia following the induction of endotoxin tolerance. SOCS1 knockdown using short hairpin RNA partly inhibited the anti-inflammatory process and promoted the inflammatory response during endotoxin tolerance. The results of the current study indicate that miR-155 inhibition contributes to the development of endotoxin tolerance. Understanding how miRs regulate inflammatory mechanisms may facilitate the development of novel therapeutic strategies to treat CNS disorders.
