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LncRNA IDH1-AS1 sponges miR-518c-5p to suppress proliferation of epithelial ovarian cancer cell by targeting RMB47

The Journal of Biomedical Research 2024年第1期38卷 51-65页

作者： Juan Zhou Yiran Xu Luyao Wang Yu Cong Ke Huang Xinxing Pan Guangquan Liu Wenqu Li Chenchen Dai Pengfei Xu Xuemei Jia Department of Gynecology Women's Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu 210004China Nanjing Maternity and Child Health Medical Institute Women's Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu 210004China.

Long noncoding RNA(lncRNA)IDH1 antisense RNA 1(IDH1-AS1)is involved in the progression of multiple cancers,but its role in epithelial ovarian cancer(EOC)is ***,we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR(qPCR).We first evaluated the effects of IDH1-AS1 on the proliferation,migration,and invasion of EOC cells through cell counting kit-8,colony formation,EdU,transwell,wound-healing,and xenograft *** then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter,qPCR,rescue experiments,and Western *** found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial *** IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis,because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of ***1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell *** miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 ***,we found that RNA binding motif protein 47(RBM47)was the downstream target of miR-518c-5p,that upregulation of RBM47 inhibited EOC cell proliferation,and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 *** together,IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.

关键词： lncRNA IDH1-AS1 epithelial ovarian cancer miR-518c-5p RBM47

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Overexpression and Immunosuppressive Functions of Transforming Growth Factor 1,Vascular Endothelial Growth Factor and Interleukin-10 in epithelial ovarian cancer

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Chinese Journal of cancer Research 2012年第2期24卷 130-137页

作者： Chan-zhen Liu Li Zhang Xiao-hong Chang Ye-xia Cheng Hong-yan Cheng Xue Ye Tian-yun Fu Jun Chen Heng Cui Gynecology Oncology Center Peking University People's HospitalBeijing 100044China

Objective： Transforming growth factor-1 （TGF-βI）, vascular endothelial growth factor （VEGF）, and interleukin-lO （IL-10） may be critical cytokines in the microenvironment of a tumor, playing roles in immune suppression. This study was conducted to elucidate the roles and immunosuppressive functions of these cytokines in epithelial ovarian cancer （EOC）. Methods： The expression levels of TGF-β1, VEGF and IL-10 in malignant tissue were evaluated by immune- histochemistry and compared with corresponding borderline, benign, and tumor-free tissues. Moreover, relationships among the levels of these cytokines and correlations between expression and the prognosis of EOC were analyzed by Pearson rank correlations and multi-factor Logistic regression. The roles of TGF-βI, VEGF, and IL-lO in the immunosuppressive microenvironment of ovarian cancer were studied through dendritic cell （DC） maturation and CD4＋CD25＋FoxP3＋ Treg generation in vitro experiments. Results： TGF-β1, VEGF, and IL-IO were expressed TGF-β1 was an independent prognostic factor for EOC n 100%, 74.69%, and 54.96% of EOC patients, respectively. L-IO was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β31 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-IO that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs. Conclusions： TGF-βI, VEGF and IL-IO play important roles in EOC and can lead to frequent immune evasion events.

关键词： epithelial ovarian cancer Tumor microenvironment Immunosuppression Cytokines

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Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of epithelial ovarian cancer Cells by Inhibiting Apoptosis

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Biomedical and Environmental Sciences 2021年第6期34卷 465-477页

作者： LI Min DONG Xu Dong LYU Qiu Bo ZHANG Wei HUANG Shuai YANG Chun Xue CUI Di LAI Hui Ying Department of Obstetrics and Gynecology Beijing Hospital National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Department of Obstetrics the First People's Hospital of Yunnan ProvinceKunming 650032YunnanChina Department of Pathology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Peking University Health Science Center Beijing 100069China Clinical Laboratory Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective To investigate the molecular mechanism of high phosphorylation levels of cofilin-1(p-CFL-1)associated with paclitaxel resistance in epithelial ovarian cancer(EOC)*** Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA *** inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8(CCK-8)*** was assessed by flow cytometry and protein levels were detected by western *** real-time polymerase chain reaction(qRT-PCR)was used to measure the expression levels of phosphokinases and phosphatases of *** analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1(SSH-1).Results High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of ***3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy,as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein *** accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial ***-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 ***,the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC *** The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.

关键词： Cofilin-1 Slingshot-1 epithelial ovarian cancer Chemo-resistance Apoptosis

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Loss of 4.1N in epithelial ovarian cancer results in EMT and matrix-detached cell death resistance

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Protein & Cell 2021年第2期12卷 107-127页

作者： Dandan Wang Letian Zhang Ajin Hu Yuxiang Wang Yan Liu Jing Yang Ningning Du Xiuli An Congying Wu Congrong Liu Department of Pathology School of Basic Medical SciencesThird HospitalPeking University Health Science CenterBeijing 100191China Institute of Systems Biomedicine Beijing Key Laboratory of Tumor Systems BiologySchool of Basic Medical SciencesPeking University Health Science CenterPeking UniversityBeijing 100191China College of Life Science Zhengzhou UniversityZhengzhou 450051China Red Cell Physiology Laboratory New York Blood CenterNew YorkNY 10065USA

epithelial ovarian cancer(EOC)is one of the leading causes of death from gynecologic cancers and peritoneal dissemination is the major cause of death in patients with *** the loss of 4.1N is associated with increased risk of malignancy,its association with EOC remains *** explore the underlying mechanism of the loss of 4.1N in constitutive activation of epithelial-mesenchymal transition(EMT)and matrixdetached cell death resistance,we investigated samples from 268 formalin-fixed EOC tissues and performed various in vitro and in vivo *** report that the loss of 4.1N correlated with progress in clinical stage,as well as poor survival in EOC *** loss of 4.1N induces EMT in adherent EOC cells and its expression inhibits anoikis resistance and EMT by directly binding and accelerating the degradation of 14-3-3 in suspension EOC ***,the loss of 4.1N could increase the rate of entosis,which aggravates cell death resistance in suspension EOC ***,xenograft tumors in nude mice also show that the loss of 4.1N can aggravate peritoneal dissemination of EOC ***-agent and combination therapy with a ROCK inhibitor and a 14-3-3 antagonist can reduce tumor spread to varying *** results not only define the vital role of 4.1N loss in inducing EMT,anoikis resistance,and entosis-induced cell death resistance in EOC,but also suggest that individual or combined application of 4.1N,14-3-3 antagonists,and entosis inhibitors may be a promising therapeutic approach for the treatment of EOC.

关键词： epithelial ovarian cancer 4.1N EMT anoikis entosis

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Mouse models of epithelial ovarian cancer for preclinical studies

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Zoological Research 2021年第2期42卷 153-160页

作者： Sergey Karakashev Ru-Gang Zhang Immunology Microenvironment&Metastasis ProgramThe Wistar InstitutePhiladelphiaPA 19104USA

epithelial ovarian cancer(EOC) is the leading cause of gynecological cancer-related mortality in the developed world. EOC is a heterogeneous disease represented by several histological and molecular subtypes. Therefore, exploration of relevant preclinical animal models that consider the heterogenic nature of EOC is of great importance for the development of novel therapeutic strategies that can be translated clinically to combat this devastating disease. In this review, we discuss recent progress in the development of preclinical mouse models for EOC study as well as their advantages and limitations.

关键词： epithelial ovarian cancer Patientderived xenografts Orthotopic mouse model Subcutaneous mouse model Intraperitoneal mouse model Syngeneic mouse model Genetic engineered mouse model

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Regulatory Effect of E2,IL-6 and IL-8 on the Growth of epithelial ovarian cancer Cells

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Cellular & Molecular Immunology 2005年第5期2卷 365-372页

作者： Yue Wang Jie Yang Yan Gao Yongrui Du Leyuan Bao Wenyan Niu Zhi Yao Department of Immunology Tianjin Medical University Tianjin 300070 China Department of Gynecologic Oncology Tianjin Women＇s Hospital Tianjin 300070 China Corresponding to： Dr. Zhi Yao Department of Immunology Tianjin Medical University 22 Qixiangtai Road Tianjin 300070 China

To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer （OVCA）, we first examined the status of estrogen receptors （ERα and ERβ）, IL-6 receptor （IL-6Rα and gp130）, and IL-8 receptor （IL-8RA and IL-8RB） on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells. Those OVCA ceUs expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol （E2）, IL-6 and IL-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner. Tamoxifen （Txf）, an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or/and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG. Taken together, our results suggested that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect.

关键词： estrogen IL-6 IL-8 cell proliferation epithelial ovarian cancer

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Adjuvant Chemotherapy May Not Be Necessary for Women with Stage IC1 epithelial ovarian cancer

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Current Medical Science 2022年第1期42卷 192-200页

作者： Dong-mei DENG Qiu-yue LIAO Jie YANG Jing CHEN Ge CHEN Hua-lin BAI Bo ZHANG Ke-zhen LI Department of Gynecology and Obstetrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:To determine whether adjuvant chemotherapy improves the prognoses in women with stage IC1 epithelial ovarian cancer(EOC).Methods:All eligible women diagnosed with stage IC1 EOC from 2003 to 2019 in Tongji Hospital were *** characteristics,tumor features,surgical types,and chemotherapeutic treatments were ***-Meier analysis and Cox regression analysis were performed to evaluate progression-free survival(PFS)and overall survival(OS).

关键词： adjuvant chemotherapy epithelial ovarian cancer intraoperative rupture overall survival progression-free survival

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Establishment of an optimized CTC detection model consisting of EpCAM,MUC1 and WT1 in epithelial ovarian cancer and its correlation with clinical characteristics

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Chinese Journal of cancer Research 2022年第2期34卷 95-108页

作者： Tongxia Wang Yan Gao Xi Wang Junrui Tian Yuan Li Bo Yu Cuiyu Huang Hui Li Huamao Liang David M.Irwin Huanran Tan Hongyan Guo Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Laboratory Medicine and Pathobiology University of TorontoToronto M5S1A8Canada

Objective:Emerging studies have demonstrated the promising clinical value of circulating tumor cells(CTCs)for diagnosis,disease assessment,treatment monitoring and prognosis in epithelial ovarian ***,the clinical application of CTC remains restricted due to diverse detection techniques with variable sensitivity and specificity and a lack of common ***:We enrolled 160 patients with epithelial ovarian cancer as the experimental group,and 90 patients including 50 patients with benign ovarian tumor and 40 healthy females as the control *** enriched CTCs with immunomagnetic beads targeting two epithelial cell surface antigens(EpCAM and MUC1),and used multiple reverse transcription-polymerase chain reaction(RT-PCR)detecting three markers(EpCAM,MUC1 and WT1)for *** then we used a binary logistic regression analysis and focused on EpCAM,MUC1 and WT1 to establish an optimized CTC detection ***:The sensitivity and specificity of the optimized model is 79.4%and 92.2%,*** specificity of the CTC detection model is significantly higher than CA125(92.2%vs.82.2%,P=0.044),and the detection rate of CTCs was higher than the positive rate of CA125(74.5%vs.58.2%,P=0.069)in early-stage patients(stage I and II).The detection rate of CTCs was significantly higher in patients with ascitic volume≥500 mL,suboptimal cytoreductive surgery and elevated serum CA125 level after 2 courses of chemotherapy(P<0.05).The detection rate of CTC;and CTC;was significantly higher in chemo-resistant patients(26.3%vs.11.9%;26.4%vs.13.4%,P<0.05).The median progression-free survival time for CTC;patients trended to be longer than CTC;patients,and overall survival was shorter in CTC;patients(P=0.043).Conclusions:Our study presents an optimized detection model for CTCs,which consists of the expression levels of three markers(EpCAM,MUC1 and WT1).In comparison with CA125,our model has high specificity and demonstrates better diagnostic values,especi

关键词： Circulating tumor cells epithelial ovarian cancer optimized detection model diagnosis and prognosis

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Expression and mechanism of action of miR-196a in epithelial ovarian cancer

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Asian Pacific Journal of Tropical Medicine 2016年第11期9卷 1082-1087页

作者： Bo Yang Sheng-Ze Li Ling Ma Hong-Li Liu Jian Liu Jun-Jun Shao Department of Female Tumor First Affiliated Hospital of Bengbu Medical College

Objective:To explore the expression,biological function and possible mechanism of action of microRNA molecular-196a(miR-196a) in epithelial ovarian ***:RT-PCR was used to detect the expression quantities of epithelial ovarian tissue,benign ovarian tissue,normal ovary epithelial tissue,ovarian cancer cell lines and miR-196 a in normal ovarian epithelial cells to analyze the relationship between the expression of miR-196 a and the clinical pathologic parameters of ovarian *** those cell lines,the cell line of which miR-196 a expressed the most or least was selected and transfected the ovarian cancer cell line by using negative control plasma and miR-196 a *** transfection,RT-PCR was used to test the expression quantity of miR-196 a,Transwell chamber method was applied to determine the migration and invasion abilities of ovarian carcinoma cells and Western blot was employed to detect the expression of HOXA10 ***:The relative expression quantities of miR-196 a in ovarian cancer tissue and benign ovarian tissue were significantly higher than that in normal ovarian epithelial tissue,and the expression quantity of miR-196 a in ovarian cancer tissue was distinctively higher than that in benign ovarian tissue(P epithelial ovarian cancer,the expression quantities of miR-196 a in patients with low differentiation were all significantly higher than those in patients with high differentiation(P 0.05).Compared with normal ovarian epithelial cell line IOSE80,the expression quantities of miR-196 a of all ovarian cancer cell lines increased obviously and differences were statistically significant(P ovarian cancer cell line SKOV3 was the highest,while it decreased significantly(4.678 ± 0.785 vs.2.131 ± 0.345,t = 2.938,P < 0.

关键词： MiR-196a epithelial ovarian cancer Migration Invasion HOXA 10

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Identification of Novel epithelial ovarian cancer Biomarkers by Cross-laboratory Microarray Analysis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第3期30卷 354-359页

作者：蒋学锋朱涛杨洁李双叶双梅廖书杰孟力卢运萍马丁 Molecular cancer Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

The purpose of this study was to pool information in epithelial ovarian cancer by combining studies using Affymetrix expression microarray datasets made at different laboratories to identify novel *** microarray expression information across laboratories was screened and combined after preprocessing raw microarray data,then ANOVA and unpaired T test statistical analysis was performed for identifying differentially expressed genes(DEGs),followed by clustering and pathway analysis for these *** this work,we performed a combination analysis on microarrays from three different laboratories using gene expression data on ovarian cancer and obtained a list of differential expression profiles identified as potential candidate in aggressiveness of ovarian *** clustering and pathway analysis explored the different molecular basis of different ovarian cancer stages and potential important regulatory pathways in ovarian cancer *** results showed that combination of microarray data from different laboratories in the same platforms may overcome biases derived from probe design and technical features,thereby accelerating the identification of trustworthy DEGs,and demonstrating the advantage of integrative analysis in gene expression studies on epithelial ovarian cancer research.

关键词： epithelial ovarian cancer biomarkers microarray analysis

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