RESUMO
Dysregulation of long noncoding RNA (LncRNA) FENDDR has been shown to be closely related to the progression of several cancers. However, its role and upstream regulatory mechanism in endometrioid endometrial carcinoma (EEC) remains unclear. This study was conducted using the cancerous tissues of EEC patients (n = 60), EEC cell lines, and a xenograft mouse model. The expression level of LncRNA FENDRR was decreased and the N-methyladenosine (m6A) methylation levels of LncRNA FENDRR was elevated in cancerous tissues of EEC patients. In vitro experiments demonstrated that YTH domain-containing 2 (YTHDF2), an m6A reader, recognized the abundance of m6A-modified LncRNA FENDRR in EEC cells and promoted its degradation. LncRNA FENDRR overexpression suppressed cell proliferation and facilitated cell apoptosis in the EEC cell line HEC-1B by reducing the protein level of SRY-related HMG box transcription factor 4 (SOX4). Interference of LncRNA FENDRR reversed the inhibitory effect of sh-YTHDF2 on cell proliferation and the promoting effect of sh-YTHDF2 on cell apoptosis in HEC-1B cells by silencing FENDRR. Finally, in vivo experiments confirmed that overexpression of LncRNA FENDRR retarded the growth of EEC cells. In conclusion, YTHDF2-mediated LncRNA FENDRR degradation promotes cell proliferation by elevating SOX4 expression in EEC.
Assuntos
Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Fatores de Transcrição SOXC/metabolismoRESUMO
Accumulating evidence suggested that tumor-associated macrophages played crucial roles in the progression of endometrial cancer. The aim of this study was to determine the role of lncRNA NIFK-AS1 in M2-like polarization of macrophages and further to investigate the effect of NIFK-AS1 modulating macrophage polarization on the proliferation, migration and invasion of endometrial cancer cells. Human peripheral blood mononuclear cells and tumor-associated macrophages were isolated from healthy volunteers and endometrial cancer patients, respectively. The expression of NIFK-AS1 and miR-146a were detected by qRT-PCR in tumor-associated macrophages or THP-1 monocytes differentiated macrophages. The expression of NIFK-AS1 and miR-146a were decreased and increased in tumor-associated macrophages of endometrial cancer patients, respectively. NIFK-AS1 overexpression suppressed the IL-4-induced M2 polarization of THP-1 macrophages. Moreover, we found that NIFK-AS1 overexpression inhibited the 17ß-estradiol-induced proliferation, migration and invasion of endometrial cancer cells through suppressing M2-like polarization of macrophages. NIFK-AS1 could interact with miR-146a and increased the expression of Notch1 through downregulating miR-146a. Further experiments revealed that miR-146a overexpression attenuated the effect of NIFK-AS1 on suppressing the M2 polarization of macrophages and the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. These findings indicated that NIFK-AS1 inhibited the M2-like polarization of macrophages via targeting miR-146a, thereby reducing the estrogen-induced proliferation, migration and invasion of endometrial cancer cells. Our study highlights the important role of NIFK-AS1 in regulating the polarization and function of tumor-associated macrophages in endometrial cancer and provides novel insight into the TAMs-mediated progression of endometrial cancer.
Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Macrófagos/citologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Sequência de Bases , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Macrófagos/imunologia , Receptor Notch1/genéticaRESUMO
LncRNA homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) has been confirmed to be involved in the tumorigenic progression of endometrial carcinoma (EC). However, the molecular mechanisms of HOTAIR in EC are not fully elucidated. The expression of HOTAIR and miR-646 in human EC tissues was determined by qRT-PCR. The effect of miR-646 on EC cells was assessed by the cell viability, migration, and invasion using CCK-8 assays and transwell assays. RNA-binding protein immunoprecipitation assays and RNA pull-down assays were performed to explore the interaction between HOTAIR and miR-646. The regulation of miR-646 on nucleophosmin 1 (NPM1) was tested using luciferase reporter assays. MiR-646 expression was significantly decreased both in human EC tissues ( n = 23) and cell lines (Ishikawa and HEC-1-A) compared with the control. Moreover, miR-646 expression was negatively related to HOTAIR in human EC tissues ( n = 23). Our results also showed that miR-646 overexpression considerably attenuated the E2-promoted viability, migration, and invasion of Ishikawa and HEC-1-A cells in vitro. In addition, HOTAIR was confirmed to regulate the viability, migration, and invasion of EC cells through negative regulating miR-646. More importantly, we also demonstrated that NPM1 was the target of miR-646, and HOTAIR promoted NPM1 expression through interacting with miR-646 in EC cells. Taken together, our findings presented that HOTAIR could regulate NPM1 via interacting with miR-646, thereby governing the viability, migration, and invasion of EC cells.
Assuntos
Movimento Celular/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Estradiol/farmacologia , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Nucleares/genética , Nucleofosmina , RNA Longo não Codificante/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVES: Cervical cancer is one of the most common gynecologic malignant tumors. Propofol has been proposed to play a role of antitumor in various cancers. However, the functions and mechanisms of Propofol in cervical cancer is still not clear. METHODS: In vitro, the different concentrations of propofol were co-incubated with cervical cancer cell lines, including Hela, Caski and C-33A cells respectively. The pcDNA-HOTAIR plasmid was transfected into cells after the treatment of 10 µg/ml propofol. The cell viability and apoptosis were detected by MTT assay and TUNEL method. In vivo, propofol was injected into mice of transplantation tumor with Caski cells or with pcDNA-HOTAIR treated Caski cells. RESULTS: Propofol significantly decreased the cell viability and increased the cell apoptosis in Hela, Caski and C-33A cells, while HOTAIR overexpression promoted cell viability and inhibits cell apoptosis. mTOR/p70S6K protein expression levels were also markedly reduced by propofol but the effects were reversed with pcDNA-HOTAIR. In vivo, propofol inhibited the tumor size but had no inhibition effect in HOTAIR overexpression group. CONCLUSION: Propofol inhibited tumor size, cell viability and promoted cell apoptosis via inhibiting mTOR/p70S6K pathway mediated by HOTAIR in cervical cancer.
Assuntos
Apoptose/efeitos dos fármacos , Propofol/administração & dosagem , RNA Longo não Codificante/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias do Colo do Útero/patologiaRESUMO
This study explored the effects of a classical Chinese medicine formula- Xiao-Chai-Hu Tang(XCHT) on the model mice with D-galactosamine -induced liver injury. Sixty male imprinting control region (ICR) mice were used in the present study, and they were separated randomly into 6 groups: a normal control group (Group A, n=10), a model control (Group B, n=10), a positive control (Group C, n=10), a low dose of XCHT group (Group D, n=10), a medium dose of XCHT group (Group E, n=10), and a high dose of XCHT group (Group F, n=10). ELISA was used to detect the IL-6 and TNF-α levels in the serum. Real-time PCR was performed to assess the expression of FasmRNA, Fas-LmRNA, Bcl-2mRNA of the liver tissues. Western blotting was used to detect the Bax protein expression of the liver tissues. The serum IL-6 and TNF-α levels of Group B were significantly higher than the other groups (P<0.05). The expression of Fas mRNA, Fas-LmRNA, and Bax protein of the liver tissues of Group B were significantly higher than those of the other groups (P<0.05). The expression of Bcl-2 mRNA of the liver tissues of Group B was significantly lower than other groups (P<0.05). Both of XCHT and biphenyl dicarboxylate significantly decreased the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increased the Bcl-2 mRNA expression of the liver tissues of model mice (P<0.05). It may be through decreasing the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increasing the Bcl-2 mRNA expression of the liver tissues that XCHT significantly relieved the D-galactosamine -induced liver injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado/efeitos dos fármacos , Magnoliopsida , Fitoterapia , Animais , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Galactosamina , Interleucina-6/sangue , Fígado/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
BACKGROUND: Candidal balanoposthitis (CB) is a common male genital infection. Autoimmune mechanisms may play an important role in the pathogenesis of CB. Interleukin-2 (IL-2) is an important molecule in cell-mediated immunity. METHODS: One hundred and one patients were diagnosed with CB using mycology culture in the dermatology and urology clinics in our hospital. Ninety-four healthy males were randomly selected as controls. We studied serum levels of IL-2 of patients with CB using ELISA and analyzed the correlations between serum IL-2 and clinical data. RESULTS: Serum IL-2 concentrations in CB patients were significantly lower than that in the control group ((7.80 ± 4.78) vs. (15.44 ± 7.90) ng/L; t = 2.27, P < 0.05). The incidence of CB in the low-level group was significantly higher than that in the high-level group (70% (71/101) vs. 36% (30/84), P < 0.05). Low levels of serum IL-2, comorbidity with other sexually transmitted diseases (STDs), and sexual partners with vulvovaginal candidiasis (VVC) increased the risk of CB. CONCLUSION: The pathogenesis of CB is a complex procedure that includes internal autoimmune factors.
Assuntos
Balanite (Inflamação)/sangue , Balanite (Inflamação)/microbiologia , Candidíase/sangue , Interleucina-2/sangue , Adulto , Idoso , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION AND HYPOTHESIS: The objective of this study is to compare the efficacy and safety of tension-free vaginal tape (TVT) with Marshall-Marchetti-Krantz (MMK) procedure in stress urinary incontinence (SUI) treatment. METHODS: Two hundred twenty-eight patients were enrolled in this study. TVT procedure was performed in 105 cases, MMK procedure was performed in 81 cases, Chi-square test was used, and P < 0.01 was considered statistically significant. RESULTS: The short-term success rate was about 89% in MMK group. However, the success rate fell to 68.2% at 5 years and 32% at 10 years. The short-term cure rate of TVT procedure was about 90.0%, and the 5-year cure rate was 84.3%. CONCLUSIONS: The short-term cure rate in both groups was similar, but the long-term success rate of the MMK procedure decreased sharply with time. The TVT technique provides long-term cure rates of over 84% with minimal complications. Patients who underwent TVT experienced shorter operation time, less blood loss, and less hospital stay.
Assuntos
Procedimentos Cirúrgicos em Ginecologia/métodos , Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
The objective of this study was to examine the effects of Chinese medicine formula-Yu Zhang Dan (YZD, composed of Herba Lysimachiae, Rhizoma Polygoni Cuspidati, Radix Curcumae) on the model rats with hepatic fibrosis. Forty male Sprague-Dawley (SD) rats were used in the present study, and they were separated randomly into 4 groups: a normal control group (Group A, n=5), a model control (Group B, n=15), a high dose of YZD (Group C, n=10), and a low dose of YZD (Group D, n=10). Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl(4)). The variation of the serum alanine transaminase (ALT), aspartate aminotransferase (AST), hyaluronate acid (HA), laminin (LN), type ⢠⢠procollagen peptide (P⢠â¢NP), L-Glutathione (GSH) was respectively measured with radioimmunoassay (RIA) and detection of transforming growth factor-beta 1 (TGF-ß1) and smooth muscle alpha actin (α-SMA) was conducted with immunohistochemistry. The ALT, AST HA, LN and PIII NP levels in the serum of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the ALT, AST HA, LN and PIII NP levels of the model rats (P<0.05). The TGF-ß1 and α-SMA levels of the model control group were significantly higher than those of the normal control group (P<0.05), and both of the high dose of YZD and low dose of YZD significantly decreased the TGF-ß1 levels of the model rats (P<0.05) , and only the high dose of YZD significantly decreased the α-SMA levels of the model rats (P<0.05). The expression of TGF-ß1 and α-SMA in the liver tissues of the rats were in the cytoplasm of the cells. It may be through decreasing the ALT, AST, HA, LN and PIII NP levels in the serum of the model rats and decreasing the expression of TGF-ß1 and α-SMA in the liver tissues of the model rats that YZD significantly relieved the hepatic fibrosis.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Tetracloreto de Carbono , Medicamentos de Ervas Chinesas/farmacologia , Ácido Hialurônico/sangue , Imuno-Histoquímica , Fígado/metabolismo , Cirrose Hepática Experimental/metabolismo , Masculino , Medicina Tradicional Chinesa , Radioimunoensaio , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1RESUMO
OBJECTIVE: To investigate the effects of sex hormones on bladder and mechanism thereof. METHODS: Sixty mature female SD rats underwent bilateral ovariectomy and then randomly divided into 6 groups: low dose estrogen group (OVX + E group) treated with estradiol benzoate 0. 25 mg/kg injected intramuscularly qod, high dose estrogen group (OVX + E 1 mg group) treated with estradiol benzoate 1 mg/kg, progesterone (P) group, treated with P 1 mg, OVX + E + P group treated with estradiol benzoate 0.25 mg/kg + progesterone 1 mg, d androgen group (OVX + T group) treated with testosterone propionate 3 mg/kg, and untreated ovariectomized group (OVX group) receiving no medication. Another 10 rats underwent sham operation. Four weeks later the rats were killed with their bladders and urethras taken out to undergo light and electron microscopy. RESULTS: The thickness of bladder wall of the OVX group was (0.97 +/- 0.11) mm, significant thinner than that of the sham operation group [(1.10 +/- 0.1) mm, P < 0.05)]. The thickness levels of bladder walls of the OVX + E and OVX + T groups were (1.23 +/- 0.12) mm and (1.26 +/- 0.12 mm) respectively, both significantly thicker than that of the OVX group (both P < 0.01). Wider spaces between the detrusor muscle fascicles and degeneration of detrusor muscle cells were seen in the bladder walls of the OVX group, and such phenomena were milder in the OVX + E and OVX + T groups, however, wider spaces between the detrusor muscle fascicles could be seen in the OVX + E + P group too. The hypertrophic effect on the detrusor muscle of the OVX + E 1 mg group was weaker than that of the OVX + E group, a lot of cytoplasmic vacuoles was seen in the 2 groups treated with E, especially the OVX + E 1 mg group. The bladder structure of the OVX + P group was similar to that of the OVX group. CONCLUSION: Endogenous testosterone level as well as estrogen level can significantly affect the bladder structure with a hypertrophic effect on bladder detrusor muscle. But higher doze of estrogen also has some unexpected effects which may destroy bladder structure. In addition, progesterone can compromise the effect of estrogen.
Assuntos
Estradiol/farmacologia , Propionato de Testosterona/farmacologia , Bexiga Urinária/efeitos dos fármacos , Animais , Estradiol/sangue , Estrogênios/farmacologia , Feminino , Tamanho do Órgão , Ovariectomia , Ratos , Ratos Sprague-Dawley , Propionato de Testosterona/sangue , Uretra/efeitos dos fármacos , Uretra/patologia , Uretra/fisiopatologia , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologiaRESUMO
OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of urinary neurofibrosarcoma. METHODS: Clinical data of 1 case of urinary neurofibrosarcoma was analyzed retrospectively and related literature reviewed. The 61-year old male patient had undergone TURP for benign prostate hyperplasia ten months before. RESULTS: Total urethral cavernostomy, total cystectomy and ileal cystostomy were performed on the patient and pathological diagnosis pointed to urinary neurofibrosarcoma. Another operation was done for metastatic rectal mass, which revealed abdominal metastasis. With progressing consumptive constitution, the patient died 40 days after the second operation. CONCLUSION: It is difficult to make a definite diagnosis in urinary neurofibrosarcoma, and the effective treatment for this highly malignant disease needs to be further studied.