Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Exp Cell Res ; 388(1): 111815, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911152

RESUMO

Extracellular vesicular long noncoding RNAs (lncRNAs) to influence recipient cells is emerging as a novel mechanism for disease progression. TC0101441 is a newly identified metastasis-related lncRNA involved in cancer. Since endometriosis exhibits prometastasis behavior similar to those observed in cancer, we aimed to investigate whether TC0101441 is involved in endometriosis and, if so, whether extracellular vesicular TC0101441 contributes to the migration/invasion of endometriotic cyst stromal cells (ECSCs). Clinically, we found that TC0101441 was highly expressed in ectopic endometria than in the eutopic and normal endometria. Serum extracellular vesicular TC0101441 levels were substantially increased in patients at stage III/IV endometriosis in comparison with stage I/II endometriosis and controls. In vitro, using TC0101441-high-expression ECSCs (ECSCs-H) as extracellular vesicles (EVs)-generating cells and TC0101441-low-expression ECSCs (ECSCs-L) as recipient cells, we observed that the PKH67-labeled ECSCs-H-derived EVs were effectively internalized by ECSCs-L. ECSCs-H-derived EVs shuttling TC0101441 were transferred to ECSCs-L, modulating their migratory/invasive abilities partially by regulating certain metastasis-related proteins, which eventually facilitated endometriosis migration/invasion. This study elucidates a potential crosstalk between ECSCs via EVs in endometriotic milieus, suggests a novel mechanism for endometriosis migration/invasion from the perspective of the "extracellular vesicular transfer of lncRNAs" and highlights the potential of circulating extracellular vesicular TC0101441 as a biomarker for endometriosis.

2.
Arch Gynecol Obstet ; 300(6): 1633-1636, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31667605

RESUMO

OBJECTIVE: To compare using the acellular porcine small intestinal submucosa (SIS) graft or the Interceed in patients with MRKH syndrome undergoing creation of a neovagina. METHODS: In this retrospective study, patients with MRKH syndrome undergoing creation of a neovagina from 2016 to 2018 were retrospectively investigated. Wharton-Sheares-George neovaginoplasty was performed using the acellular porcine SIS graft or the Interceed. RESULTS: Overall, 67 patients were included for analysis. The operating time, the estimated blood loss and return of bowel activity were similar between the two groups. However, the total cost in the SIS group was significantly higher than that in the Interceed group due to the cost of the SIS graft. The mean length and width of the neovagina were similar between the two groups. However, the incidence of granulation in vaginal apex was higher in the SIS graft group than that in the Interceed group. There was no statistically significant difference in the total FSFI scores between the two groups who became sexually active postoperatively. CONCLUSIONS: Our results demonstrated that Wharton-Sheares-George method provided the patients to have satisfactory sexual intercourse. The Interceed played a role in the reconstruction of neovagina no less than the SIS graft.

3.
Int J Cancer ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577838

RESUMO

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

4.
Onco Targets Ther ; 12: 7699-7711, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571921

RESUMO

Purpose: Exosomes are key mediators of cellular communication by transporting molecules, including long noncoding RNAs (lncRNAs), and have been regarded as promising non-invasive biomarkers. This study aimed to evaluate the expression pattern and clinical significance of serum exosomal lncRNA antisense hypoxia inducible factor (aHIF) in epithelial ovarian cancer (EOC). Patients and methods: Sixty-two EOC patients in Obstetrics and Gynecology Hospital of Fudan University were enrolled. The expression levels of aHIF in tissues and serum exosomes were examined by RT-qPCR. The origin of serum exosomal aHIF was explored in vitro and in vivo. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic factors of EOC. A prognostic predictive nomogram was formulated in R software. Results: We isolated exosomes, identified exosomal aHIF in the serum of EOC patients. The expression of serum exosomal aHIF was higher in EOC patients and was correlated with the aHIF level in EOC tissues. In vitro and in vivo, the results indicated that serum exosomal aHIF was derived from tumor cells. Kaplan-Meier survival analysis demonstrated that EOC patients with higher serum exosomal aHIF expression had poorer overall survival. Cox multivariate regression model revealed that FIGO stage, residual tumor size, and serum exosomal aHIF level were independent prognostic factors of EOC. Based on the prognostic value of serum exosomal aHIF, we established a nomogram model that showed a good predictive ability for EOC patients. Conclusion: Serum exosomal aHIF is overexpressed in EOC and can serve as a noninvasive predictive biomarker for unfavorable prognosis.

5.
Onco Targets Ther ; 12: 6145-6156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496722

RESUMO

Purpose: The long noncoding RNA LINC00673 has emerged as an important regulator of cancer development and progression. However, the clinical significance and biological roles of LINC00673 in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to explore the oncogenic roles and underlying molecular mechanisms of LINC00673 in EOC. Patients and methods: The expression levels of LINC00673 in EOC tissues and cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Real-time cellular analysis (RTCA), flow cytometry, and transwell assays were conducted to investigate cell proliferation, apoptosis, migration and invasion in vitro. Subcutaneous transplanted tumors were established to explore the oncogenic role of LINC00673 in vivo. Differentially expressed genes were analyzed using transcriptome sequencing. Protein levels were determined by Western blot assays. Results: LINC00673 was upregulated in EOC tissues and cell lines compared to their corresponding normal controls. High expression of LINC00673 was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, serous histological subtype, lymph node metastasis and poor prognosis in patients with EOC. LINC00673 was also identified as an independent prognostic factor for EOC. In addition, LINC00673 promoted cell migration, invasion and proliferation and inhibited cell apoptosis in vitro and induced tumor growth in vivo. Mechanistically, opioid growth factor receptor (OGFR) was found to be a potential downstream target gene that mediated the oncogenic effect of LINC00673 in EOC. Conclusion: LINC00673 contributes to EOC proliferation and metastasis and may be a promising prognostic biomarker for EOC patients.

6.
J Cancer ; 10(8): 1930-1940, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205552

RESUMO

Although accumulating evidence suggests that long non-coding RNAs (lncRNAs) are critical determinants of ovarian cancer development and progression, reports of metastasis-associated lncRNAs are limited. Here, we focused on NONHSAT076754 and explored its expression level, clinical value, biological behavior and molecular basis in epithelial ovarian cancer (EOC) metastasis. The results showed that NONHSAT076754 expression was increased in EOC tissues and cell lines and that this expression was closely related with FIGO stage, high tumor grade and lymph node metastasis. Furthermore, NONHSAT076754 knockdown markedly inhibited EOC cell migration and invasion in vitro. Consistently, the in vivo data from both the bioluminescence imaging and tumor dissection revealed that depletion of NONHSAT076754 reduced EOC metastasis. Mechanically, the pro-metastatic activities of NONHSAT076754 were partially regulated by PTEN and HTATIP2. Further rescue assays validated that knockdown of HTATIP2 remarkably reversed NONHSAT076754 silencer-induced inhibition of EOC cell metastasis. These data indicate that NONHSAT076754 is a vital regulator of EOC metastasis, laying the foundation for lncRNA-based clinical management of EOC aggressiveness and metastasis.

7.
Exp Cell Res ; 381(2): 215-222, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085188

RESUMO

Endometriosis, a common gynecological disease, is associated with pelvic pain and infertility. Endometriosis affects approximately 10% of women, but that number increases to 30-50% in symptomatic premenopausal women. Despite the prevalence of endometriosis, the cause has yet to be fully elucidated. Recent study of the molecular pathways of endometrial cancer has brought the long non-coding RNA (lncRNA) H19 to our attention. In this paper, we explored the role of lncRNA-H19 in endometrial tissue proliferation. We found that ectopic endometrial cells taken from women with endometriosis showed elevated levels of lncRNA-H19, with expression levels correlating to disease progression. Knockdown of H19 in ectopic endometrial cells inhibited cell proliferation and invasion. Coinciding with this change was an increase in microRNA-124-3p (miR-124-3p) and a decrease in integrin beta-3 (ITGB3) levels. The addition of a miR-124-3p inhibitor mitigated this decrease in ITGB3. Up-regulation of miR-124-3p markedly suppressed ITGB3 expression by binding to the 3' untranslated region (3' UTR), while inhibition of miR-124-3p had the opposite effect. ITGB3 overexpression potently counteracted the effects of miR-124-3p mimics on ectopic endometrial cells. From these results, we can infer that in endometriosis both miR-124-3p and ITGB3 operate as downstream effector proteins in the H19-signaling pathway. Down-regulation of lncRNA-H19 could inhibit ectopic endometrial cell proliferation and invasion by modulating miR-124-3p and ITGB3, offering a novel target for treatment.

8.
Reprod Sci ; 26(12): 1590-1602, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30808247

RESUMO

OBJECTIVE: The transfer of long noncoding RNAs (lncRNAs) via exosomes to modulate recipient cells represents an important mechanism for disease progression. Antisense hypoxia-inducible factor (aHIF) is a well-known angiogenesis-related lncRNA. Here, we aimed to investigate the clinical implications of aHIF and exosomal aHIF in endometriosis and the involvement of exosome-shuttled aHIF in endometriosis angiogenesis. STUDY DESIGN: The distribution and expression of aHIF in ectopic, eutopic, and normal endometria was evaluated. Serum exosomal aHIF levels in patients with endometriosis were tested. The correlation between serum exosomal aHIF and aHIF expression in ectopic endometria was analyzed. Endometriotic cyst stromal cells (ECSCs)-derived exosomes were characterized. The internalization of exosomes by human umbilical vein endothelial cells (HUVECs) was observed. A series of in vitro assays were conducted to investigate the roles and mechanisms of exosomal aHIF in endometriosis angiogenesis. RESULTS: Clinically, aHIF was highly expressed in ectopic endometria and serum exosomes in patients with endometriosis. Serum exosomal aHIF was significantly correlated to aHIF expression in matched ectopic endometria. In vitro, PKH67-labeled exosomes derived from aHIF high expression ECSCs were effectively internalized by recipient HUVECs. Notably, exosome-shuttled aHIF was transferred from ECSCs to HUVECs, which in turn elicited proangiogenic behavior in HUVECs by activating vascular endothelial growth factor (VEGF)-A, VEGF-D, and basic fibroblast growth factor, thereby facilitating endometriosis angiogenesis. CONCLUSION: Our study illustrates a potential cell-cell communication between ECSCs and HUVECs in an ectopic environment, provides a novel mechanistic model explaining how ECSCs induce angiogenesis from the perspective of the "exosomal transfer of aHIF," and highlights the clinical value of circulating exosomal aHIF in endometriosis.

9.
Biomed Pharmacother ; 112: 108695, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30797154

RESUMO

To elucidate the potential function of lncRNA SNHG3 in the development of osteosarcoma. Quantitative real-time polymerase chain reaction was conducted for detection of SNHG3, miRNA-151a-3p and RAB22 A in osteosarcoma tissues and cells. Receiver operating characteristic curve was introduced to analyze the diagnostic potential of SNHG3 in osteosarcoma. Correlation between SNHG3 expression and the overall survival of osteosarcoma patients was evaluated using Kaplan-Meier method. Invasive and migratory potentials of osteosarcoma cells were examined by Transwell assay. Furthermore, dual-luciferase reporter gene assay, RNA-pull down and RIP assay were used to verify the binding of SNHG3/RAB22 A to miRNA-151a-3p. The function of SNHG3/miRNA-151a-3p/RAB22 A axis in osteosarcoma was finally confirmed by rescue experiments. SNHG3 and RAB22 A were highly expressed in osteosarcoma patients, while miRNA-151a-3p was lowly expressed. The overall survival of osteosarcoma patients with high expression of SNHG3 was shorter than those with low expression. SNHG3 overexpression markedly promoted invasive and migratory potentials of osteosarcoma cells. Through dual-luciferase reporter gene assay, both SNHG3 and RAB22 A could bind to miRNA-151a-3p. RAB22 A expression was positively regulated by SNHG3, but negatively regulated by miRNA-151a-3p. Finally, rescue experiments confirmed that RAB22 A overexpression could reverse the promotive effects of miRNA-151a-3p knockdown on invasive and migratory potentials of osteosarcoma cells. SNHG3 is highly expressed in osteosarcoma, and promotes the invasive and migratory potentials of osteosarcoma cells by absorbing miRNA-151a-3p to upregulate RAB22 A expression.


Assuntos
Movimento Celular/fisiologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Osteossarcoma/metabolismo , RNA Longo não Codificante/biossíntese , Proteínas rab de Ligação ao GTP/biossíntese , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Proteínas rab de Ligação ao GTP/genética
10.
Onco Targets Ther ; 11: 9101-9110, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588022

RESUMO

Purpose: Hypoxia is a key stress that triggers apoptosis in various tumors, including epithelial ovarian cancer (EOC). Previous researches identified a hypoxia-upregulated lncRNA named "a natural antisense transcript of hypoxia-inducible factor 1 (aHIF)" in some tumors. However, the contribution of aHIF to EOC remains unclear. Here, we aimed to investigate the expression, function, and underlying mechanisms of aHIF in EOC progression under hypoxia. Materials and methods: Expression levels of aHIF in EOC tissues were tested. In vitro and in vivo assays were conducted to explore the function and mechanism of aHIF in hypoxia-induced EOC progression. Results: aHIF levels were increased in EOC tissues and were upregulated by hypoxia in EOC cells. Functional data revealed that aHIF knockdown accelerated cell apoptosis under hypoxia and inhibited EOC tumorigenesis and tumor growth in vivo. Additionally, aHIF overexpression inhibited cell apoptosis and enhanced cell proliferation under hypoxia in EOC. Mechanistically, the dysregulation of certain key mitochondrial apoptosis pathway-related genes, including Bcl-2, Bax, Caspase-7, and Caspase-9, may partially explain aHIF-regulated EOC apoptosis and growth under hypoxia. Conclusion: These data provide the first convincing evidence that aHIF may inhibit EOC apoptosis and thereby promote tumor growth through activation of the mitochondrial apoptosis pathway under hypoxia. Our findings help clarify the role of lncRNA in hypoxia-induced EOC progression.

11.
Int J Biol Sci ; 14(14): 1960-1973, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30585260

RESUMO

Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Exossomos/metabolismo , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Adenocarcinoma de Pulmão/genética , Animais , Western Blotting , Exossomos/genética , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Análise Multivariada , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Biosci Trends ; 12(4): 342-353, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30146551

RESUMO

Gynecologic cancer is a vital global healthcare issue with high rates of mortality and morbidity. Tumor metastasis attributes to most of the death suffering from solid tumors. The epithelial-mesenchymal transition (EMT) plays a pivotal role in initiating metastasis. Long non-coding RNAs (lncRNAs), a well-known group of non-coding RNAs, and a prominent topic in life science research, are misregulated in many malignancies and some are EMT-associated. In the case of gynecologic cancers, several EMT-associated lncRNAs have been identified and found to be implicated in cancer aggressiveness and progression. Mechanically, these lncRNAs participate in the EMT-related metastatic process in multiple ways including interaction with polycomb repressive complex 2 (PRC2), regulation of EMT signaling networks, mediation of EMT-transcription factors (EMT-TFs) and EMT markers, and cooperation with microRNAs (miRNAs). Further studies on these EMT-associated lncRNAs and identification of more relevant lncRNAs are imperative for the lncRNAs-based clinical management of high rate of metastasis in patients with gynecologic cancers.


Assuntos
Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias dos Genitais Femininos/fisiopatologia , RNA Longo não Codificante/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/fisiopatologia , Feminino , Neoplasias dos Genitais Femininos/genética , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/fisiopatologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/fisiopatologia
13.
Biochem Biophys Res Commun ; 502(4): 493-500, 2018 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-29859193

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. LncRNA has been confirmed to participate in a variety of cancers. The purpose of this study was to explore the effect of FOXP4-AS1 on the development of osteosarcoma (OS) and its underlying mechanism. FOXP4-AS1 expressions in 60 OS tissues and paracancerous tissues were detected by qRT-PCR (quantitative real-time polymerase chain reaction). We confirmed that FOXP4-AS1 was overexpressed in OS tissues than that of paracancerous tissues. The disease-free survival and overall survival of OS patients were not correlated with age, gender and tumor location, but remarkably correlated with FOXP4-AS1 expression, tumor size and lung metastasis. For in vitro experiments, MG63 cells expressed a higher expression of FOXP4-AS1, whereas U2OS cells expressed a lower expression, which were selected for the following studies. Overexpressed FOXP4-AS1 led to enhanced proliferation, migration and invasion, shortened G0/G1 phase, as well as inhibited cell cycle. Knockdown of FOXP4-AS1 in MG63 cells obtained the opposite results. Furthermore, RIP assay indicated that FOXP4-AS1 could inhibit LATS1 expression by binding to LSD1 and EZH2, so as to participate in OS development. In conclusion, these results revealed that FOXP4-AS1 is overexpressed in OS, and is the independent risk factor in OS prognosis. Upregulated FOXP4-AS1 promotes the proliferation, migration and cell cycle, but inhibits apoptosis of OS cells. Furthermore, FOXP4-AS1 participates in the development and progression of OS by downregulating LATS1 via binding to LSD1 and EZH2.


Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histona Desmetilases/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Masculino , Osteossarcoma/patologia , PTEN Fosfo-Hidrolase/genética , Ligação Proteica , Adulto Jovem
14.
Arch Gynecol Obstet ; 297(3): 775-784, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29362924

RESUMO

PURPOSE: Ovarian conservation is controversial in patients with cervical adenocarcinoma due to the risk of ovarian metastasis. The aim of this study is to evaluate the association of ovarian conservation with survival outcomes in young patients with T1N0M0 cervical adenocarcinoma. METHODS: Women who were 45 years of age or younger with T1N0M0 cervical adenocarcinoma from 1988 to 2013 recorded in the Surveillance, Epidemiology, and End Results (SEER) database were included. Propensity score weighting was used to balance the intragroup differences. Cause-specific survival (CSS) and overall survival (OS) were compared using Kaplan-Meier estimates. A multivariate Cox model was used to adjust for covariates including propensity score. A stratified analysis was then conducted. RESULTS: Totally, 1090 (79.7%) patients underwent oophorectomy and 278 (20.3%) patients whose ovaries were preserved were identified. Patients with preserved ovaries were younger, with a lower T classification and less likely to undergo pelvic lymphadenectomy (all p < 0.05). After propensity weighting, ovarian conservation group had better cause-specific survival (CSS) (5-year 98.8 versus 97.1%, 10-year 98.0 versus 95.2%, p = 0.0370) and overall survival (OS) (5-year 98.8 versus 97.1%, 10-year 96.5 versus 93.5%, p = 0.0025). After adjustment, the CSS benefit of ovarian conservation was marginally significant (p = 0.051) and OS benefit was still significant (p = 0.006). Stratified analysis showed that the CSS benefit was found in T1b classification (HR, 0.23; 95% CI 0.06-0.89, p = 0.033) and histological grade > 1 (HR 0.12; 95% CI 0.02-0.87; p = 0.035). CONCLUSION: Among young women with T1N0M0 cervical adenocarcinoma, ovarian conservation is associated with better survival.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma Adenoescamoso/cirurgia , Tratamentos com Preservação do Órgão , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Bases de Dados Factuais , Feminino , Preservação da Fertilidade/métodos , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ovariectomia , Ovário/patologia , Ovário/cirurgia , Vigilância da População , Pontuação de Propensão , Sistema de Registros , Programa de SEER , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
15.
Oncol Rep ; 39(3): 1034-1042, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29286125

RESUMO

Gonadotropins, including luteinizing hormone (LH) and follicle stimulating hormone (FSH), are conducive to the growth of ovarian cancer based on the 'gonadotropin theory' and are regulated by gonadotropin-releasing hormone (GnRH). The present study was carried out to investigate the effect of goserelin, a GnRH agonist, on the apoptosis of epithelial ovarian cancer (EOC) cells and the underlying in vitro and in vivo mechanisms. Through flow cytometry, Hoechst staining and TUNEL staining, we demonstrated that goserelin promoted the apoptosis of EOC cells both in vitro and in vivo. Through human apoptosis gene PCR array, we verified that the promotion of EOC cell apoptosis by goserelin was linked to the upregulation of members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, which have been identified as downstream targets of forkhead box O1 (FOXO1). Goserelin enhanced FOXO1 expression, and siRNA-mediated knockdown of FOXO1 abrogated the induction of apoptosis by goserelin. Moreover, goserelin decreased AKT activity, and FOXO1 upregulation by goserelin was dependent on the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. In vivo, the expression of key factors in the PI3K/AKT/FOXO1 pathway was consistent with that observed in vitro. In conclusion, our data suggested that goserelin may promote EOC cell apoptosis by upregulating FOXO1 through the PI3K/AKT signaling pathway. We believe that GnRH agonists may be potential antitumor agents, and key factors in the PI3K/AKT-FOXO1 pathway may also be novel therapeutic targets for the treatment of EOC.


Assuntos
Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Proteína Forkhead Box O1/metabolismo , Gosserrelina/farmacologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antineoplásicos Hormonais/farmacologia , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Proliferação de Células/efeitos dos fármacos , Feminino , Proteína Forkhead Box O1/genética , Humanos , Camundongos , Camundongos Nus , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Sci Rep ; 7(1): 4469, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28667302

RESUMO

Long non-coding RNA RAD51 antisense RNA 1 (RAD51-AS1, also known as TODRA) has been shown to be down-regulated by E2F1, a key cell cycle and apoptosis regulator, in breast cancer. Little is known regarding the role of RAD51-AS1 in disease. Here, we investigate the role of RAD51-AS1 in epithelial ovarian cancer (EOC). Using luciferase reporter and chromatin immunoprecipitation experiments, we verified RAD51-AS1 as a target of E2F1 under negative regulation in EOC. We then examined RAD51-AS1 expression in EOC samples using in situ hybridization (ISH). RAD51-AS1 was localized to the nucleus and found to be a critical marker for clinical features that significantly correlated with poor survival in EOC patients. RAD51-AS1 was also an independent prognostic factor for EOC. Overexpression of RAD51-AS1 promoted EOC cell proliferation, while silencing of RAD51-AS1 inhibited EOC cell proliferation, delayed cell cycle progression and promoted apoptosis in vitro and in vivo. RAD51-AS1 may participate in carcinogenesis via regulation of p53 and p53-related genes. Our study highlights the role of RAD51-AS1 as a prognostic marker of EOC. Based on its regulation of the tumor suppressor p53, RAD51-AS1-based therapy may represent a viable therapeutic option for EOC in the near future.


Assuntos
Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Antissenso/genética , RNA Longo não Codificante/genética , Rad51 Recombinase/genética , Adulto , Idoso , Apoptose/genética , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Ligação Proteica , Transporte Proteico , Rad51 Recombinase/metabolismo , Carga Tumoral , Proteína Supressora de Tumor p53/metabolismo
17.
Int J Oncol ; 51(2): 507-514, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28714515

RESUMO

Previously, the novel oestrogen (E2)-upregulated lncRNA TC0101441, was identified by us, via microarray analysis. However, the detailed mechanism by which E2 upregulates TC0101441 and the role of TC0101441 in epithelial ovarian cancer (EOC) progression have not been elucidated. In the present study, we further analysed TC0101441, which we designated oestrogen-induced long non-coding RNA-1 (ElncRNA1). We showed that E2 transcriptionally upregulates ElncRNA1 through the oestrogen receptor α (ERα)-oestrogen response element (ERE) pathway using RNA stability assays, bioinformatics-based searches for ERE binding sites, chromatin immunoprecipitation (ChIP) assays and dual luciferase reporter assays. Clinically, ElncRNA1 levels are significantly higher in EOC tissues than in normal ovarian surface epithelium. In vitro and in vivo loss-of-function assays revealed that ElncRNA1 promotes EOC cell proliferation. This pro-proliferation effect of ElncRNA1 was partially mediated by the regulation of CDK4, CDK6 and cyclin D1. These findings provide the first evidence that E2 upregulates ElncRNA1 at the transcriptional level through the ERα-ERE pathway and that this novel E2-upregulated lncRNA has an oncogenic role in EOC growth. The placement of ElncRNA1 in the E2-ERα-ERE signalling pathway may provide greater insight into the effects of oestrogen on EOC progression from the perspective of lncRNA.


Assuntos
Receptor alfa de Estrogênio/genética , Estrogênios/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Regulação para Cima , Animais , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Transplante de Neoplasias , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Estabilidade de RNA , RNA Longo não Codificante/química
18.
Tumour Biol ; 37(10): 14193-14203, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27553024

RESUMO

Paraoxonase (PON) enzymes possess antioxidant properties and protect against cardiovascular diseases. As a member of PON family, PON3 is primarily synthesized in the liver and poorly investigated. This study aimed to examine the expression of PON3 in human hepatocellular carcinoma (HCC) and investigate the clinical significance and biological function of PON3 in HCC patients. We first analyzed PON3 expression in 50 paired HCC samples (HCC tissues vs matched para-cancerous tissues) and 160 clinical HCC specimens by using immunohistochemistry (IHC). Our results showed that the expression of PON3 was downregulated in HCC and significantly associated with tumor-node-metastasis (TNM) stage, tumor size, and tumor number. Kaplan-Meier survival and Cox regression analyses showed that PON3 was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR). Finally, we aimed to reveal the biological function of PON3 in HCC growth and metastasis, and our results showed that overexpression of PON3 potently inhibited growth and metastasis of HCC. Collectively, our study demonstrated that PON3 exhibited tumor-suppressive effects toward HCC and it might serve as a novel prognostic marker in HCC.


Assuntos
Arildialquilfosfatase/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/patologia , Animais , Apoptose , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Oncotarget ; 7(37): 58931-58938, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-27391344

RESUMO

Over-expression of long non-coding RNA (lncRNA)-CLMAT3 is significantly associated with colorectal liver metastasis and is an independent predictor of poor survival for colorectal cancer patients. However, as little is known regarding the role of this gene in the proliferation of colorectal cancer in vitro, we investigated the involvement of lncRNA-CLMAT3 in colorectal cancer cell proliferation. In this study, we demonstrate that lncRNA-CLMAT3 expression was significantly increased in colorectal cancer cells compared with a normal intestinal mucous cell line and that inhibition of lncRNA-CLMAT3 suppressed colorectal cancer cell proliferation in vitro. We also found that this reduced colorectal cancer cell proliferation due to lncRNA-CLMAT3 knockdown is associated with G0/G1 cell-cycle arrest induction and apoptosis enhancement. Furthermore, lncRNA-CLMAT3 knockdown enhanced Cdh1 expression and resulted in p27Kip accumulation via increased Skp2 protein ubiquitination. Taken together, our findings suggest that reducing lncRNA-CLMAT3 inhibits colorectal cancer cell proliferation by affecting cell cycle components.


Assuntos
Neoplasias Colorretais/genética , Mucosa Intestinal/metabolismo , RNA Longo não Codificante/genética , Antígenos CD , Apoptose , Caderinas/genética , Caderinas/metabolismo , Ciclo Celular , Proliferação de Células , Neoplasias Colorretais/terapia , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Mucosa Intestinal/patologia , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas , Ubiquitinação
20.
Oncotarget ; 7(22): 32478-92, 2016 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-27095571

RESUMO

Antisense non-coding RNA in the INK4 locus (ANRIL) has been implicated in a variety of cancers. In the present study, we evaluated ANRIL expression in epithelial ovarian cancer (EOC) and defined its clinical implications and biological functions. ANRIL was overexpressed in EOC tissues relative to normal controls. Overexpression correlated with advanced International Federation of Gynecologists and Obstetricians stage and high histological grade. Multivariate analysis indicated that ANRIL is an independent prognostic factor for overall survival in EOC. Gain- and loss-of-function experiments demonstrated that ANRIL promotes EOC cell proliferation both in vitro and in vivo. The proliferative effect was linked to the promotion of cell cycle progression and inhibition of apoptosis and senescence. Down-regulation of P15INK4B and up-regulation of Bcl-2 by ANRIL may partially explain ANRIL-induced EOC cell proliferation. This study is the first to establish that ANRIL promotes EOC progression and is a potential prognostic biomarker.


Assuntos
Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/genética , Animais , Apoptose/genética , Carcinoma Epitelial do Ovário , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Senescência Celular/genética , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA