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1.
Front Surg ; 10: 1052133, 2023.
Article in English | MEDLINE | ID: mdl-36843991

ABSTRACT

Vulvar adhesions are defined as partial or complete adherence of the labia minora and/or labia majora. Vulvar adhesions are rare, especially in postmenopausal women.This article describes a case of postmenopausal recurrent vulvar adhesions successfully treated with surgery. The patient was a 52-year-old woman who had undergone manual separation and surgical adhesion release due to vulvar adhesions, which recurred soon after treatment. The patient then came to our hospital for treatment because of complete dense adhesions to the vulva and laboured urination. The patient received surgical treatment, the anatomical structure of the vulva recovered well, and the symptoms affecting the urinary system disappeared. There was no readhesion during the 3-month follow-up.

2.
Front Oncol ; 12: 1003222, 2022.
Article in English | MEDLINE | ID: mdl-36408178

ABSTRACT

A growing attention has been attached to the role of fatty acid metabolism (FAM) in the development of cancer, and cervical cancer (CC) is still the primary cause of cancer-associated death in women worldwide. Therefore, it is imperative to explore the possible prognostic significance of FAM in CC. In this study, CC samples and corresponding normal samples were acquired from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Single sample gene set enrichment analysis (ssGSEA) was conducted for calculating FAM-related scores (FAMRs) to screen FAM-related genes (FAMRGs). Two subtypes related to FAM were identified by consistent clustering. Among them, subtype C2 had a poor prognosis, and C1 had a high level of immune cell infiltration, while C2 had a high possibility of immune escape and was insensitive to chemotherapy drugs. Based on the differentially expressed genes (DEGs) in the two subtypes, a 5-gene signature (PLCB4, FBLN5, TSPAN8, CST6, and SERPINB7) was generated by the least absolute shrinkage and selection operator (LASSO) and Akaike information criterion (AIC). The model demonstrated a high prognostic accuracy (area under the curve (AUC)>0.7) in multiple cohorts and was one independent prognostic factor for CC patients. Accordingly, FAMRGs can be adopted as a biomarker for the prediction of CC patients' prognosis and help guide the immunotherapy of CC.

3.
Front Endocrinol (Lausanne) ; 13: 858176, 2022.
Article in English | MEDLINE | ID: mdl-35784569

ABSTRACT

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation. Methods: The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis. Results: Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression. Conclusion: Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.


Subject(s)
Endometriosis , Animals , Aromatase/genetics , Aromatase/metabolism , Autophagy , Endometriosis/metabolism , Endometriosis/prevention & control , Endometrium/pathology , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogens/metabolism , Estrogens/pharmacology , Female , Gallic Acid/analogs & derivatives , Humans , Mice , Receptors, Progesterone/metabolism , Stromal Cells/metabolism , Stromal Cells/pathology , Tumor Necrosis Factor-alpha/metabolism
4.
Article in English | MEDLINE | ID: mdl-35673991

ABSTRACT

Polymersomes (or polymer vesicles) have attracted much attention for biomedical applications in recent years because their lumen can be used for drug delivery and their coronas and membrane can be modified with a variety of functional groups. Thus, polymersomes are very suitable for improved antibacterial and anticancer therapy. This review mainly highlighted recent advances in the synthetic protocols and design principles of intelligent antibacterial and anticancer polymersomes. Antibacterial polymersomes are divided into three categories: polymersomes as antibiotic nanocarriers, intrinsically antibacterial polymersomes, and antibacterial polymersomes with supplementary means including photothermal and photodynamic therapy. Similarly, the anticancer polymersomes are divided into two categories: polymersomes-based delivery systems and anticancer polymersomes with supplementary means. In addition, the bilateral relationship between bacteria and cancer is addressed, since more and more evidences show that bacteria may cause cancer or promote cancer progression. Finally, prospective on next-generation antibacterial and anticancer polymersomes are discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.


Subject(s)
Drug Delivery Systems , Neoplasms , Anti-Bacterial Agents/therapeutic use , Drug Carriers/chemistry , Drug Delivery Systems/methods , Humans , Nanomedicine/methods , Neoplasms/drug therapy , Polymers/chemistry
5.
Ann Med ; 53(1): 1502-1508, 2021 12.
Article in English | MEDLINE | ID: mdl-34431412

ABSTRACT

Objectives: Early fetal demise (absence of cardiac activity in a visible fetus) is a very common event, but there are no reliable biomarkers to predict it. The purpose of the study was to assess the association of platelet parameters with early fetal demise.Methods: In this case-control study, we included women with normal deliveries or those ultrasound diagnosed as early fetal demise. For those who were identified with early fetal demise, the platelet parameters were analyzed before the ultrasound diagnosis, which is based on the absence of either an embryo within a gestational sac or cardiac activity in a visible embryo in the 5-10 weeks of gestation. The association between the risk of early fetal demise with the women's mean platelet volume (MPV) and platelet counts was calculated by logistic regression. Duplicate measurements of platelet aggregation were performed with VerifyNow. Results: In total, 99 women identified with early fetal demise and 170 women who had an uncomplicated pregnancy with normal delivery from January 2017 and August 2020 were included in the study. We found that platelet counts in the early fetal demise group were significantly higher than healthy pregnancies. In addition, platelet reactivity is higher in the normal delivery group than those in early fetal demise group (p < .05). High levels of platelet counts resulted in an adjusted odds ratio (OR) of 2.075 (95% confidence interval [95% CI], 1.215-3.544; p = .008) for early fetal demise. Conclusions: Increased platelet counts in the first trimester may be a predictor for the risk of early fetal demise.


Subject(s)
Fetal Death , Fetal Heart/diagnostic imaging , Gestational Sac/diagnostic imaging , Platelet Count , Pregnancy Complications/blood , Pregnancy/blood , Ultrasonography, Prenatal , Adult , Case-Control Studies , China/epidemiology , Female , Fetal Heart/embryology , Humans , Pregnancy Trimester, First , Time Factors
6.
Front Genet ; 12: 679643, 2021.
Article in English | MEDLINE | ID: mdl-34178037

ABSTRACT

BACKGROUND: Secondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear. MATERIALS AND METHODS: An endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-ß1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFßR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson's trichrome. RESULTS: ADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-ß1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-ß1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFßR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-ß1-induced ESC injury model. The miR-150-5p mimic promoted TGF-ß1-induced ESC fibrosis. CONCLUSION: ADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis.

7.
Front Genet ; 12: 775006, 2021.
Article in English | MEDLINE | ID: mdl-35003215

ABSTRACT

In recent years, the incidence and mortality of cervical cancer have increased worldwide. At the same time, increasing data have confirmed that miRNA-mRNA plays a positive or negative regulatory role in many cancers. This study attempted to screen effective miRNA-mRNA in the progression of cervical cancer, and to study the mechanism of miRNA-mRNA in the progression of cervical cancer. The expression profile data of GSE7410, GSE 63514, GSE 86100 and TCGA-CESC were downloaded, and 34 overlapping differentially expressed genes (22 up-regulated and 12 down-regulated) and 166 miRNAs (74 down-regulated and 92 up-regulated) were screened through limma package. Then, miR-197-3p/TYMS pairs were obtained by PPI, functional enrichment, Kaplan-Meier plotter analysis, Cox univariate and multivariate analysis, risk modeling, WGCNA, qPCR and dual-luciferase experiments. The results showed that TYMS was an independent prognostic factor of cervical cancer, and its expression level was negatively correlated with cervical cancer tissue grade (TMN), tumor grade, age, microsatellite stability and tumor mutation load, and positively correlated with methyl expression in DNMT1, DNMT2, DNMT3A and DNMT3B. Functional experiments showed that TYMS knockout could promote the proliferation, migration and invasion of HeLa cells and reduce apoptosis. Overexpression of TYMS showed the opposite trend, miR-197-3p was negatively correlated with the expression of TYMS. MiR-197-3p inhibitor reversed the effect of si-TYMS on the proliferation of HeLa cells. In conclusion, these results reveal that TYMS plays a very important role in the prognosis and progression of cervical cancer, and has the potential to be thought of as cervical cancer biomarkers. At the same time, miR-197-3p/TYMS axis can regulate the deterioration of cervical cancer cells, which lays a foundation for the molecular diagnosis and treatment of cervical cancer.

8.
Ann Palliat Med ; 9(4): 1606-1613, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32648453

ABSTRACT

BACKGROUND: In vitro fertilization-embryo transfer is a main assisted reproductive technique that can improve the success rate of conception. At present, the ultrasound-guided oocyte retrieval is often employed in clinics, but this process will cause pain and fear in outpatients. This study explored the safety and satisfaction of patients who received egg retrieval under vaginal topical tetracaine anesthesia combined with intravenous propofol anesthesia. METHODS: Patients who underwent elective egg retrieval in the Reproductive Center of Shanghai Tenth People's Hospital were recruited from January 2017 to August 2018 [tetracaine + propofol group (n=53); propofol group (n=48)]. RESULTS: Results showed that tetracaine combined with propofol anesthesia could effectively reduce the dose of propofol during surgery, ensure the quality of follicles, effectively reduce the postoperative pain and improve the operational satisfaction without affecting the prognosis. CONCLUSIONS: Our findings provide evidence for further clinical applications of this technique.


Subject(s)
Anesthetics, Intravenous/therapeutic use , Oocyte Retrieval/methods , Propofol , Tetracaine/therapeutic use , China , Female , Fertilization in Vitro , Humans , Propofol/therapeutic use
9.
Ecotoxicol Environ Saf ; 201: 110726, 2020 Sep 15.
Article in English | MEDLINE | ID: mdl-32480160

ABSTRACT

BACKGROUND: Impaired in utero fetal growth trajectory may have long term health consequences of the newborns and increase risk of adulthood metabolic diseases. Prenatal exposure to air pollution has been linked to fetal development restriction; however, the impact of exposure to ambient air pollutants on the entire course of intrauterine fetal development has not been comprehensively investigated. METHODS: During 2015-2018, two cohorts of mother-infant dyads (N = 678 and 227) were recruited in Shanghai China, from which three categories of data were systematically collected: (1) daily exposure to six air pollutants during pregnancy, (2) fetal biometry in the 2nd (gestational week 24, [GW24]) and 3rd trimester (GW36), and (3) neonatal outcomes at birth. We investigated the impact of prenatal exposure to air pollutant mixture on the trajectory of fetal development during the course of gestation, adjusting for a broad set of potential confounds. RESULTS: Prenatal exposure to PM2.5, PM10, SO2 and O3 significantly reduced fetal biometry at GW24, where SO2 had the most potent effect. For every 10 µg/m3 increment increase of daily SO2 exposure during the 1st trimester shortened femur length by 2.20 mm (p = 6.7E-21) translating to 5.3% reduction from the average of the study cohort. Prenatal air pollution exposure also decreased fetal biometry at GW36 with attenuated effect size. Comparing to the lowest exposed quartile, fetus in the highest exposed quartile had 6.3% (p = 3.5E-5) and 2.1% (p = 2.4E-3) lower estimated intrauterine weight in GW24 and GW36, respectively; however, no difference in birth weight was observed, indicating a rapid catch-up growth in the 3rd trimester. CONCLUSIONS: To our knowledge, for the first time, we demonstrated the impact of prenatal exposure to ambient air pollutants on the course of intrauterine fetal development. The altered growth trajectory and rapid catch-up growth in associated with high prenatal exposure may lead to long-term predisposition for adulthood metabolic disorders.


Subject(s)
Air Pollutants/toxicity , Fetal Development/drug effects , Maternal Exposure/adverse effects , Particulate Matter/toxicity , Adult , Air Pollutants/chemistry , China/epidemiology , Cohort Studies , Female , Gestational Age , Humans , Infant, Newborn , Particulate Matter/chemistry , Pregnancy
10.
Zygote ; 27(6): 367-374, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31452481

ABSTRACT

Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/ß (ERα, ERß) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.


Subject(s)
Adipose Tissue/cytology , Endometrium/injuries , Stem Cell Transplantation/methods , Stem Cells/cytology , Tissue Adhesions/therapy , Uterine Diseases/therapy , Wounds and Injuries/therapy , Animals , Cells, Cultured , Endometrium/metabolism , Female , Humans , Infertility/etiology , Infertility/therapy , Rats, Sprague-Dawley , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tissue Adhesions/etiology , Uterine Diseases/etiology , Wounds and Injuries/complications
11.
Am J Transl Res ; 11(5): 3081-3091, 2019.
Article in English | MEDLINE | ID: mdl-31217877

ABSTRACT

microRNAs play important roles in proliferation and differentiation of stem cells, but mechanisms by which microRNAs regulate osteogenic or adipogenic differentiation of adipose stem cells (ASCs) are still poorly understood. In the present study, results showed up-regulation of microRNA-196a was able to promote the osteogenic differentiation of ACSs, but down-regulation of microRNA-196a induced adipogenic differentiation. Further investigation indicated microRNA-196a could regulate Wnt signaling pathway to affect osteogenic or adipogenic differentiation of ASCs, addition of Wnt agonist 1 was able to reverse the down-regulated osteogenic differentiation of ASCs caused by microRNA-196a deficiency and inhibition of Wnt signaling pathway with XAV939 promoted the adipogenic differentiation of ASCs. Taken together, microRNA-196a may regulate Wnt signaling pathway to promote the osteogenic differentiation and inhibit the adipogenic differentiation of ASCs.

13.
Medicine (Baltimore) ; 96(30): e7607, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28746211

ABSTRACT

This study aimed to investigate the effects of epidermal growth factor (EGF) on the proliferation and differentiation of adipose stem cells (ASC) during the repeated passaging and probe the underlying signal pathway. Results showed that the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1 phase reduced significantly, but ASCs in G2/M phase and S phase increased markedly in ASCs treated with EGF when compared with ASCs without EGF treatment, indicating that EGF made more ASCs in proliferation phase. The adipogenic capability of ASCs without EGF was compromised when compared with that of ASCs after EGF treatment, although significant difference was not observed. The osteogenic and chondrogenic potencies increased significantly in ASC with EGF treatment indicating EGF could maintain differentiative capacity of ASCs. Gene Set Enrichment Analysis showed EGF upregulated the expression of molecules in the epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA database analysis indicated the network interaction between EGF and STAT. EGF receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate the role of both pathways in these effects. After inhibition of EGFR or STAT3, the proliferation of ASCs was significantly inhibited, and Western blotting showed EGF was able to markedly increase the expression of EGFR and STAT3. These findings suggest EGF not only promotes the proliferation of ASCs and delays their senescence, but also maintains the differentiation potency of ASCs, which are related to the EGF-induced activation of STAT signal pathway.


Subject(s)
Adipocytes/metabolism , Cell Proliferation/physiology , Epidermal Growth Factor/metabolism , Multipotent Stem Cells/metabolism , STAT3 Transcription Factor/metabolism , Adipocytes/drug effects , Adipogenesis/drug effects , Adipogenesis/physiology , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/physiology , Cell Proliferation/drug effects , Cells, Cultured , Cellular Senescence/drug effects , Cellular Senescence/physiology , Chondrogenesis/drug effects , Chondrogenesis/physiology , Epidermal Growth Factor/administration & dosage , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Growth Substances/administration & dosage , Growth Substances/metabolism , Humans , Multipotent Stem Cells/drug effects , Osteogenesis/drug effects , Osteogenesis/physiology , STAT3 Transcription Factor/antagonists & inhibitors , Signal Transduction
14.
Eur J Obstet Gynecol Reprod Biol ; 214: 150-155, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28535400

ABSTRACT

OBJECTIVES: This study was designed to compare the Cervista high risk (HR) human papillomavirus (HPV) test with Luminex XMAP technology for the detection of the relationship between HPV infection and cervical intraepithelial neoplasia. METHODS: In total, 3280 patients in a cervical specialty clinic were divided into two groups for either Cervista (1855 patients) or Luminex (1425 patients). Subsequent colposcopy examinations were performed in 1270 women with cytologic results showing ASCUS or higher level lesions. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. RESULTS: The positive rates of the Cervista and Luminex groups were 61.48% and 67.43%, respectively, and occurrence in those 30-40 years old was most common. The typing of HPV showed that A9 positive cases were the most prevalent genotype (33.53%), followed by A5/A6 (16.44%) and A7 (11.37%) in the Cervista group, and HPV-16 was the most prevalent genotype (25.81%), followed by HPV-18 (18.6%) and HPV-31 (8.6%) in the Luminex group. Moreover, the overall concordance rate was 96.26% (95% confidence interval, 93.51-99.00%) in the 187 women with cytologic results of ASCUS or higher. There were no significant differences in the positive rates of HPV between the Cervista and Luminex groups, and both had a high sensitivity and NPV. CONCLUSIONS: The results showed a high good concordance between the two methods in diagnostic accuracy. Among the patients in the cervical specialty clinic, both the A9 group of HPV and HPV-16 showed the highest positive rate. Cervista and Luminex shared similar a clinical value in the detection of CIN2 or higher.


Subject(s)
DNA Probes, HPV , Reagent Kits, Diagnostic , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Uterine Cervical Neoplasms/virology , Young Adult , Uterine Cervical Dysplasia/virology
15.
Opt Express ; 25(8): 9019-9027, 2017 Apr 17.
Article in English | MEDLINE | ID: mdl-28437976

ABSTRACT

We have theoretically and experimentally demonstrated a novel approach to excite Bloch surface wave (BSW) on tapered optical fibers, which are coated with one-dimensional photonic crystal (1DPC) consisting of periodic TiO2 and Al2O3 by atomic layer deposition technology. Two resonant dips are found in transmission spectra that are originated from the excitation of BSW for p-polarized light and s-polarized light, respectively. For the first time, we have demonstrated the developed device for refractive index (RI) sensing.

16.
Sensors (Basel) ; 16(12)2016 Nov 30.
Article in English | MEDLINE | ID: mdl-27916900

ABSTRACT

We have proposed and demonstrated a Michelson interferometer-based fiber sensor for detecting acoustic emission generated from the partial discharge (PD) of the accessories of a high-voltage cable system. The developed sensor head is integrated with a compact and relatively high sensitivity cylindrical elastomer. Such a sensor has a broadband frequency response and a relatively high sensitivity in a harsh environment under a high-voltage electric field. The design and fabrication of the sensor head integrated with the cylindrical elastomer is described, and a series of experiments was conducted to evaluate the sensing performance. The experimental results demonstrate that the sensitivity of our developed sensor for acoustic detection of partial discharges is 1.7 rad / ( m ⋅ Pa ) . A high frequency response up to 150 kHz is achieved. Moreover, the relatively high sensitivity for the detection of PD is verified in both the laboratory environment and gas insulated switchgear. The obtained results show the great potential application of a Michelson interferometer-based fiber sensor integrated with a cylindrical elastomer for in-situ monitoring high-voltage cable accessories for safety work.

17.
Oncotarget ; 7(44): 72250-72262, 2016 11 01.
Article in English | MEDLINE | ID: mdl-27750218

ABSTRACT

Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines. Ino80 bound to the Nanog transcription start site (TSS) and enhanced its expression in cervical cancer cells. Nanog overexpression in Ino80 knockdown cell lines promoted cell proliferation. This study demonstrated for the first time that Ino80 was upregulated in cervical cancer and promoted cell proliferation and tumorigenesis. Our findings suggest that Ino80 may be a potential therapeutic target for the treatment of cervical cancer.


Subject(s)
Carcinogenesis/genetics , DNA Helicases/metabolism , Gene Expression Regulation, Neoplastic , Nanog Homeobox Protein/genetics , Uterine Cervical Neoplasms/genetics , ATPases Associated with Diverse Cellular Activities , Animals , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cervix Uteri/pathology , DNA-Binding Proteins , Epigenesis, Genetic , Female , Fluorescent Antibody Technique , G1 Phase Cell Cycle Checkpoints , Gene Knockdown Techniques , Humans , Mice , Mice, Nude , RNA Interference , RNA, Small Interfering/metabolism , Transcription Initiation Site , Up-Regulation , Uterine Cervical Neoplasms/pathology , Xenograft Model Antitumor Assays
18.
Mol Med Rep ; 14(3): 2465-72, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27484896

ABSTRACT

Increasing evidence suggests that the long non-coding RNA, HOX transcript antisense intergenic RNA (HOTAIR) is widely involved in the progression and metastasis of cancer. However, the specific role of HOTAIR in ovarian carcinogenesis remains to be fully elucidated. In the present study, the levels of HOTAIR were detected in 30 paired cancer and noncancer tissues using reverse transcription-quantitative polymerase chain reaction analysis. The effect of HOTAIR on the ovarian cancer cells was examined by overexpression or small interfering RNA interference experiments. To examine the competitive endogenous RNA (ceRNAs) mechanism, a luciferase reporter assay was used. In patients with ovarian cancer, HOTAIR was significantly upregulated. Furthermore, the upregulation of HOTAIR increased the proliferation, migration and invasion of ovarian cancer cells. By contrast, the knockdown of HOTAIR repressed cell invasion and viability. HOTAIR functioned as a ceRNA, and acted as a sink for microRNA (miR)­373, thereby regulating the expression of Rab22a. The upregulation of HOTAIR contributed to the malignant progression of ovarian cancer cells. Therefore, the positive regulation between HOTAIR and Rab22a can be partially attributed to the ceRNA regulatory network through miR-373.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Ovarian Neoplasms/genetics , RNA, Long Noncoding/genetics , rab GTP-Binding Proteins/genetics , Adult , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis
19.
PLoS One ; 11(2): e0148994, 2016.
Article in English | MEDLINE | ID: mdl-26910359

ABSTRACT

An improved understanding of the pluripotency maintenance of embryonic stem (ES) cells is important for investigations of early embryo development and for cell replacement therapy, but the mechanism behind pluripotency is still incompletely understood. Recent findings show that zinc, an essential trace element in humans, is critically involved in regulating various signaling pathways and genes expression. However, its role in ES cell fate determination remains to be further explored. Here we showed that 2µM zinc chloride (ZnCl2) transiently maintained mouse ES cell pluripotency in vitro. The cultured mouse ES cells remained undifferentiated under 2µM ZnCl2 treatment in leukemia inhibitory factor (LIF) withdrawal, retinoic acid (RA) or embryoid bodies (EBs) differentiation assays. In addition, ZnCl2 increased pluripotency genes expression and inhibited differentiation genes expression. Further mechanistic studies revealed that ZnCl2 transiently activated signal transducers and activators of transcription 3 (Stat3) signaling through promoting Stat3 phosphorylation. Inhibition of Stat3 signaling abrogated the effects of ZnCl2 on mouse ES cell pluripotency. Taken together, this study demonstrated a critical role of zinc in the pluripotency maintenance of mouse ES cells, as well as an important regulator of Stat3 signaling.


Subject(s)
Chlorides/pharmacology , Mouse Embryonic Stem Cells/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Zinc Compounds/pharmacology , Animals , Mice , Mouse Embryonic Stem Cells/cytology , Phosphorylation/drug effects
20.
Tumour Biol ; 2015 Aug 21.
Article in English | MEDLINE | ID: mdl-26289848

ABSTRACT

The malignancy of endometrial carcinoma (EC) largely results from its high invasive feature. The regulation of the mRNA splicing of vascular endothelial growth factor A (VEGF-A) is critical for EC-associated cancer vascularization and invasion. Recently, we have reported that poorly prognostic EC had high levels of YT521, a newly defined RNA splicing protein. However, whether YT521 may similarly regulate the splicing of VEGF-A in EC is unknown. Here, we showed that EC specimens contained significantly higher levels of YT521, compared to the adjacent non-tumor endometrial tissue. Higher levels of YT521 were detected in EC specimens with metastases. High-YT521 EC is associated with poor patient survival. In order to examine whether YT521 may regulate VEGF-A mRNA splicing in EC, we transfected an EC cell line HEC-1A with different doses of YT521 mimics. We found that YT521 dose-dependently increased the ratio of VEGF-165 vs VEGF-121 at both mRNA and protein level, suggesting that YT521 may promote VEGF-A mRNA splicing to favor a VEGF-165 isoform. Moreover, the increases in the ratio of VEGF-165 vs VEGF-121 by YT521 overexpression resulted in increases in EC cell invasion, while decreases in the ratio of VEGF-165 vs VEGF-121 by YT521 depletion resulted in decreases in EC cell invasion in a transwell cell migration assay. Further, overexpression of VEGF-165, but not overexpression of VEGF-121, increased EC cell invasiveness. Finally, a strong correlation was detected between the ratio of VEGF-165 vs VEGF-121 and the levels of YT521 in EC specimens. Together, these data suggest that YT521 may promote EC metastases by regulating mRNA splicing of VEGF-A.

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