RESUMO
Cervical carcinoma is the most common gynecological cancer in women worldwide. Emerging evidence has shown that long non-coding RNAs (lncRNAs) participate in multiple biological processes of cervical carcinoma tumorigenesis. We aimed to investigate the function of a novel lncRNA RP11-284F21.9 in cervical carcinoma. We found that RP11-284F21.9 was down-regulated in cervical carcinoma tissues and cell lines. Overexpression of RP11-284F21.9 inhibits proliferation, invasion and migration of cervical carcinoma cells in vitro. Further, we identified that RP11-284F21.9 directly interacted with miR-769-3p and functioned as the miR-769-3p sponge. Mechanistically, we showed that miR-769-3p regulated peptidylprolyl isomerase domain and WD repeat-containing protein1 (PPWD1) expression by targeting PPWD1 3'-UTR. Furthermore, xenograft tumor model revealed that overexpression of RP11-284F21.9 inhibited tumor growth of cervical carcinoma in vivo. Taken together, our results demonstrate that RP11-284F21.9 functions as tumor suppressor and regulates PPWD1 expression through competitively binding to miR-769-3p in cervical carcinoma, suggesting that RP11-284F21.9/miR-769-3p/PPWD1 axis could serve as a promising prognostic biomarker and therapeutic target for cervical carcinoma.
Assuntos
Carcinoma/genética , MicroRNAs/metabolismo , Peptidilprolil Isomerase/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Regiões 3' não Traduzidas/genética , Animais , Carcinogênese/genética , Carcinoma/patologia , Carcinoma/cirurgia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colo do Útero/patologia , Colo do Útero/cirurgia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
MicroRNAs are emerging as critical regulators in various fundamental biological processes, including tumor progression. MicroRNA-219-5p (miR-219-5p) has been suggested as a novel tumor suppressing miRNA for many types of human cancers. However, the expression and functional significance of miR-219-5p in epithelial ovarian cancer remain poorly understood. In this study, we sought to explore the potential functions of miR-219-5p in epithelial ovarian cancer. Herein, we found that miR-219-5p levels were significantly decreased in epithelial ovarian cancer tissues and cell lines. Further experiments showed that overexpression of miR-219-5p inhibited epithelial ovarian cancer cell proliferation, migration, and invasion, and suppressed the Wnt/ß-catenin signaling pathway. By contrast, suppression of miR-219-5p exhibited the opposite effects. Twist was identified as a downstream target of miR-219-5p, and its expression was directly regulated by miR-219-5p. Restoration of Twist expression in miR-219-5p-overexpresing cells significantly reversed the antitumor effects of miR-219-5p. Taken together, our results revealed a tumor suppressive role for miR-219-5p in epithelial ovarian cancer that includes suppression of cell proliferation, migration, and invasion through downregulation of the Twist/Wnt/ß-catenin signaling pathway. Our study suggests that miR-219-5p may have potential applications in the diagnosis and treatment of epithelial ovarian cancer.
Assuntos
Movimento Celular , Proliferação de Células , MicroRNAs/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Apoptose , Western Blotting , Carcinoma Epitelial do Ovário , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Células Tumorais Cultivadas , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
T-helper (Th) 17 and the more recently identified Th22 cells are of great importance in host defense against pathogens, but can also be responsible for chronic inflammatory disorders. However, the roles of the two cell subsets in syphilis remain elusive. In this study, we show that the frequencies of Th17 and Th22 cells are significantly increased in the peripheral blood of patients with secondary syphilis (SS). A significant positive correlation is observed between Th17 and Th22 cells, whereas a negative correlation exists between Th17 and Th1 cells. Moreover, the frequency of Th17 cells has a significant positive correlation with the plasma interleukin 6 (IL-6) or IL-1ß levels, and the frequency of Th22 cells is positively correlated with the IL-6 or IL-23 levels. Finally, the elevated frequencies of Th17 and Th22 cells are positively associated with plasma C-reactive protein levels. Our results suggest that Th17 and Th22 cells may be implicated in the pathogenesis of the SS.