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1.
J Mol Med (Berl) ; 100(9): 1271-1286, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35788718

RESUMO

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.


Assuntos
Neoplasias do Endométrio , MicroRNAs , RNA Longo não Codificante , beta-Arrestina 2 , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , beta-Arrestina 2/genética , beta-Arrestina 2/metabolismo
2.
Front Med (Lausanne) ; 8: 722963, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568378

RESUMO

Purpose: The aim of this study was to evaluate white blood cell (WBC) count as a risk factor related to methotrexate (MTX) treatment failure in patients with ectopic pregnancy (EP). Methods: A total of 236 women diagnosed with EP and treated with a single dose of MTX were included. The exposure variable was WBC count at baseline, and the outcome was MTX treatment outcome. Both a multivariate binary logistics regression model and subgroup analysis were performed to evaluate the association between WBC and MTX non-response. Results: WBC count was associated with the risk of treatment failure, and the odds ratio (OR) in different multivariate models was stable [minimally adjusted model: OR 1.2, 95% confidence interval (CI): 1.0-1.3, p = 0.008; fully adjusted model: OR 1.2, 95% CI: 1.0-1.4, p = 0.026]. For WBCs in group T3 (>8.9 × 109/L), the association between WBC count and treatment failure was significant (minimally adjusted model: OR: 2.0, 95% CI: 1.0-3.8, p = 0.050; fully adjusted model: OR: 2.2, 95% CI: 1.1-5.6, p = 0.034). Subgroup analysis showed that in participants with regular menstruation (OR 1.1, 95% CI: 1.0-1.3), WBC count was significantly different from irregular menstruation (OR 1.8, 95% CI: 1.2-2.8); p for interaction was 0.031. Conclusions: We found a reliable and non-linear relationship between WBC count and MTX treatment failure for EP.

3.
Front Cell Infect Microbiol ; 11: 659505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307190

RESUMO

The features of the vaginal microbiota (VM) community can reflect health status, and they could become new biomarkers for disease diagnosis. During pregnancy, domination of bacteria of the genus Lactobacillus in the VM community is regarded as a keystone because they stabilize the VM by producing antimicrobial compounds and competing adhesion. An altered VM composition provides a marker for adverse pregnancy outcomes. This nested case-control study aimed to characterize the VM in women with a tubal pregnancy (TP) presenting with pain and/or uterine bleeding in early pregnancy. Chinese women with a symptomatic early pregnancy of unknown location were the study cohort. 16S rDNA gene-sequencing of V3-V4 variable regions was done to assess the diversity, structures, taxonomic biomarkers, and classification of the VM community. The primary outcome was the location of the early pregnancy. The VM community in women with a TP showed higher diversity (PD-whole-tree, median: 8.26 vs. 7.08, P = 0.047; Shannon Diversity Index, median: 1.43 vs 0.99, P = 0.03) and showed different structures to those in women with an intrauterine pregnancy (IUP) (R = 0.23, P < 0.01). Bacteria of the genus Lactobacillus were significantly enriched in the IUP group, whereas bacteria of the genera Gardnerella and Prevotella were significantly enriched in the TP group. Lactobacillus abundance could be used to classify the pregnancy location (AUC = 0.81). Non-Lactobacillus-dominated microbiota (≤ 0.85% Lactobacillus) was significantly associated with a TP (adjusted odds ratio: 4.42, 95% confidence interval: 1.33 to 14.71, P = 0.02). In conclusion, among women with a symptomatic early pregnancy, a higher diversity and lower abundance of Lactobacillus in the VM is associated with a TP.


Assuntos
Microbiota , Gravidez Tubária , Estudos de Casos e Controles , China , Feminino , Humanos , Lactobacillus/genética , Gravidez , RNA Ribossômico 16S/genética , Vagina
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