RESUMO
We investigated the associations between Beclin-1 and microRNA-30a (miR-30a) expression and the severity and treatment response in colorectal cancer (CRC). Our sample size consisted of 139 CRC patients who were treated with surgery alone. Immunohistochemistry was used to investigate the expression and prognostic significance of Beclin-1 in CRC, while the weak expression of Beclin-1 in normal tissue was used as the basis for assessing tumors (control group). Real-time reverse transcription-polymerase chain reaction quantified miR-30a levels. The expression levels of Beclin-1 and miR-30a were associated with clinical variables and prognoses. Beclin-1 was expressed more highly in CRC tissues than in controls. This expression was related to gender (P = 0.023), histological grade (P = 0.006), M stage (P = 0.004), tumor node metastasis stage (P = 0.020), vascular invasion, and nodal involvement. Patients with higher Beclin-1 expression levels had higher survival rates (P = 0.08) than patients with lower Beclin-1 expression levels. Beclin-1 was a prognostic indicator (P < 0.05) in a multivariate analysis. Beclin-1 was overexpressed in CRC tissues and was correlated with lower levels of miR-30a (P < 0.05, r = -0. 4189). In conclusion, Beclin-1 was a good prognostic indicator in CRC and was correlated with survival rate. Beclin-1 is important in the growth and metastasis of CRC. Apoptosis in CRC might be due to the increased autophagy induced by decreased levels of miR-30a.
Assuntos
Proteína Beclina-1/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , MicroRNAs/genética , Apoptose , Autofagia , Proteína Beclina-1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
Changes in the expression of the anti-apoptotic protein cFLIP (cellular FLICE inhibitory protein) were examined in the caprine corpus luteum (CL), during development and subsequent maintenance. Corpora lutea at four different stages were collected from Shiba goats, to measure the expression of cFLIP mRNA, protein and immunolocalization. Expression of short form cFLIP (cFLIPS) mRNA was highest at the early CL stage, and decreased during late and regressed stages (P < 0.05). In contrast, long form cFLIP (cFLIPL) mRNA expression was high during early, mid and late stages, and only decreased at the regressed stage (P< 0.01). Protein expression of cFLIPS was highest at the late CL stage, and decreased at the regressed stage (P < 0.01). Protein expression of cFLIPL was highest at the early and mid CL stages, and decreased by the late and regressed stages (P < 0.01). Further expression of cFLIPL was higher at the early CL stage than at the mid stage (P < 0.01). cFLIP protein expression was detectable by immunostaining in the early, mid and late CL stages, but not at the regressed CL stage. These results are consistent with the hypothesis that cFLIP acts as a survival factor in the maintenance of CL function in goats.
Assuntos
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Corpo Lúteo/metabolismo , Ciclo Estral/genética , Ciclo Estral/metabolismo , Cabras/fisiologia , Animais , Feminino , Cabras/genética , RNA Mensageiro/genéticaRESUMO
We determined expression and localization of the anti-apoptotic cellular FLICE inhibitory protein (cFLIP) in the porcine corpora lutea (CL) and corpus albicans (CA) during estrous and pregnancy. The CL and CA were collected at different stages of estrous to determine cFLIP immunolocalization, and mRNA and protein expression. The mRNA expression of the short cFLIP isoform (cFLIPS) was higher at the early and mid CL stages, and lower by the late CL stage (P < 0.01); mRNA expression of the long cFLIP isoform (cFLIPL) was higher at the mid CL stage, and lower at the early and late CL stages (P < 0.01). Levels of cFLIPS and cFLIPL were steady and high during the early and mid CL stages, and had significantly decreased (P < 0.01) by the late stage. The cFLIP protein was highly expressed in the early and mid CL stages of estrous, but weakly ex-pressed in the late stage. Expression of cFLIPS showed no significant difference between preovulatory corpus albicans (CA1) and corpus albicans (CA2) coexistent with the CL from the previous estrus, but cFLIPL mRNA expression was higher during CA1 than CA2. The expression of cFLIPS showed no significant difference between CA1 and CA2, but cFLIPL was not detected. The cFLIP protein was weak-ly expressed in the CA. Expression of cFLIPS and cFLIPL mRNA and proteins was observed in the CL, and the cFLIP protein was highly expressed during pregnancy. We propose that cFLIPS/L acts as a survival factor, and performs an anti-apoptotic function in the porcine CL.