RESUMO
Objective: This study aimed to explore the roles and mechanisms of lncRNA FAM225B and PDIA4 in ovarian cancer. Methods: RT-qPCR and Western blot assays were performed to detect the expression levels of the lncRNAs FAM225B, DDX17, and PDIA4 in the serum of patients with ovarian cancer and cell lines. Cells were transfected with lncRNA FAM225B- and PDIA4-related vectors to determine the malignant phenotypes using functional experiments. The mutual binding of lncRNA FAM225B and DDX17 was verified using RNA pull-down and RIP assays. Results: The expression of lncRNAs FAM225B and PDIA4 was decreased in the serum of patients with ovarian cancer and cell lines. Restoration of lncRNA FAM225B or PDIA4 reduced cell proliferation, migration, and invasion abilities and elevated the apoptosis rate, whereas suppression of lncRNA FAM225B or PDIA4 exhibited an inverse trend. RNA pull-down and RIP assays revealed a direct interaction between lncRNA FAM225B and DDX17. ChIP assay revealed a relationship between DDX17 and the PDIA4 promoter. LncRNA FAM225B and DDX17 positively regulate PDIA4 expression. Downregulation of PDIA4 expression counteracts the suppressive effect of lncRNA FAM225B overexpression in ovarian cancer cells. Conclusion: This research study supports the fact that lncRNA FAM225B in ovarian cancer can upregulate PDIA4 by directly binding to DDX17, inhibiting the activities of ovarian cancer cells.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , Fatores de Transcrição , RNA Longo não Codificante/genética , Neoplasias Ovarianas/genética , Invasividade Neoplásica/genética , RNA Helicases DEAD-box/genética , Isomerases de Dissulfetos de ProteínasRESUMO
Preeclampsia (PE) is a hypertensive disorder of pregnancy. PE patients were reported to have higher serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) than those in healthy controls. However, whether the expressions of these inflammation biomarkers have a causal relationship with PE is unspecified. We applied the Mendelian randomization method to infer the causal relationship between inflammation biomarkers (e.g., CRP, IL-6, interleukin 1 receptor antagonist [IL-1ra] and TNF-α) and PE. Single nucleotide polymorphisms (SNPs) strongly related to inflammation biomarkers were used as instrumental variables. CRP, IL-1ra and IL-6 levels showed no significant effect on PE progression, while the genetic predicted higher level of TNF-α significantly increased the risk of PE (OR per 1-SD increase in TNF-α: 4.33; 95% CI [1.99, 9.39]; p = .00021). The findings suggest that pro-inflammatory activity of TNF-α could be a determinant for PE progression. More antenatal care should be given to those pregnant women with higher level of inflammation biomarkers, especially TNF-α.
Assuntos
Interleucina-6 , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Interleucina-6/genética , Fator de Necrose Tumoral alfa/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Análise da Randomização Mendeliana , Inflamação/genética , Proteína C-Reativa/genética , BiomarcadoresRESUMO
OBJECTIVE: Increased expression of KDM1A and decreased expression of DACT1 in cervical cancer cells were noticed in a previous study. This study is aimed at exploring the mechanism behind the KDM1A regulation on DACT1 in cervical cancer cells. METHODS: The expression profile of KDM1A and DACT1 in cervical cancer tissues was searched in TCGA database. In vitro experiments verified the effect of KDM1A and DACT1 on proliferation and migration ability of cervical cancer cell lines after cell transfection. The interaction of KDM1A with HDAC1 was identified by coimmunoprecipitation (Co-IP). The expression levels of KDM1A and DACT1 in cervical cancer cell lines were determined by qRT-PCR and western blot. RESULTS: TCGA database showed that cervical cancer tissues had elevated expression of KDM1A and decreased expression of DACT1, which was consistent with the observation in cervical cancer cell lines. KDM1A was found to negatively regulate DACT1 through histone deacetylation. Meanwhile, the downregulation of KDM1A or overexpression of DACT1 could suppress the cell proliferation and migration ability in HeLa and SiHa cells. Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression. CONCLUSION: KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular , Proliferação de Células , Histona Desmetilases/metabolismo , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Processamento de Proteína Pós-Traducional , Neoplasias do Colo do Útero/enzimologia , Acetilação , Proteínas Adaptadoras de Transdução de Sinal/genética , Bases de Dados Factuais , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Histona Desmetilases/genética , Humanos , Invasividade Neoplásica , Proteínas Nucleares/genética , Transdução de Sinais , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: Myocardial infarction (MI) is a major cause of cardiovascular disease which poses great healthy and financial burden for individuals. MI can be mainly induced by hypoxia. Therefore, in this study, we aimed to explore the function and mechanism of lncRNA H19 on hypoxia-induced pyroptosis of cardiomyocytes. METHOD: Peripheral blood from healthy controls and MI patients was collected for determination of mRNA and protein expression levels of H19 and CYP1B1. The correlation between these two factors was analyzed. Then MI rat model was established and injected with H19 overexpression/CYP1B1 knockdown plasmid, in which the infraction area and pathological morphology were observed. Hypoxic cardiomyocytes were transfected with overexpression or knockdown of H19 and CYP1B1 for determination of NLRP3, ASC, caspase-1, IL-1ß, IL-18, CyclinD1, and PCNA. Cell proliferation ability was assessed by CCK8. RIP and dual luciferase gene reporter assay were applied to verify the binding among H19, PBX3 and CYP1B1. RESULTS: Downregulated H19 and upregulated CYP1B1 were observed in MI patients. A negative correlation was found for H19 and CYP1B1 expressions. Transfection of H19 overexpression or CYP1B1 knockdown could attenuate the MI progression in MI rats. In hypoxic cardiomyocytes, H19 overexpression or CYP1B1 knockdown could also inhibit NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in addition to suppressing cell apoptosis rate and promoting cell proliferation rate. Different expression pattern was found in cells transfected with H19 knockdown or CYP1B1 overexpression. Overexpression of CYP1B1 could abrogate the suppressive effect of H19 on pyroptosis of cardiomyocytes. H19 could inhibit activity of CYP1B1 promoters by regulating PBX3. CONCLUSION: H19 could inhibit CYP1B1 expression in a PBX3-dependent way and thus attenuate cell pyroptosis of cardiomyocytes.