ABSTRACT
Progesterone is often used to protect the endometrium and prevent endometrial cancer. An intensive study on its molecular mechanism in endometrial cancer would contribute to the development of more promising therapies. Relevant lncRNAs and mRNAs expression data in endometrial cancer cell line Ishikawa pretreated and post-treated with progesterone were derived from Gene Expression Omnibus (accession no. GSE29435), and then we analyzed long noncoding RNAs and mRNAs with differential expressions in two different conditions. The Cytoscape software, TargetScan, miRanda, and Human microRNA Disease Database (HMDD) websites were employed. Gene set enrichment analysis (GSEA) was used to determine related Kyoto Encyclopedia of Genes and Genomes pathways alteration in Ishikawa cells treated with progesterone. In addition to bioinformatics analysis, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot, and dual-luciferase reporter assays were performed. The impact of progesterone on cell propagation and cell cycle was testified by colony formation and flow cytometry analysis. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was the most significantly downregulated lncRNA in endometrial cancer cells treated with progesterone. Lymphoid enhancing factor 1 (LEF1) was positively associated with NEAT1, and eventually hsa_miR-146b-5p was validated to target both LEF1 and NEAT1. Wnt/ß-catenin signaling pathway was identified to involve in endometrial cancer. NEAT1 or LEF1 was overexpressed in endometrial cancer cells while downregulated following post-treatment with progesterone. Conversely, miR-146b-5p was notably decreased in Ishikawa cells while upregulated after treatment with progesterone. Downstream gene c-myc or MMP9 regulated by upstream gene LEF1 in Wnt/ß-catenin signaling pathway was remarkably increased in Ishikawa cells and positively related with NEAT1. Progesterone inhibited cell cycle and viability through regulating NEAT1/miR-146b-5p axis via Wnt/ß-catenin signaling pathway. Progesterone exerted suppressive influence on endometrial cancer progression via regulation of lncRNA NEAT1/miR-146b-5p-mediated Wnt/ß-catenin signaling pathway, which might reveal new strategies for developing more effective therapeutics. © 2018 IUBMB Life, 71(1):223-234, 2019.
Subject(s)
Cell Cycle Checkpoints/drug effects , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Progesterone/pharmacology , RNA, Long Noncoding/genetics , Wnt Signaling Pathway/genetics , beta Catenin/genetics , Base Sequence , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrium/drug effects , Endometrium/metabolism , Endometrium/pathology , Female , Gene Ontology , Humans , Lymphoid Enhancer-Binding Factor 1/genetics , Lymphoid Enhancer-Binding Factor 1/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , MicroRNAs/metabolism , Molecular Sequence Annotation , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA, Long Noncoding/metabolism , Stromal Cells/drug effects , Stromal Cells/metabolism , Stromal Cells/pathology , beta Catenin/metabolismABSTRACT
OBJECTIVE: To study the clinical value of optoelectronic cervical cancer screening system (TruScreen, TS) in the screening of cervical cancer in comparison with cervical cytology test. METHODS: A total of 392 patients were screened by TS, Pap, TCT, and HPV using the pathological and colposcopical results as the golden standard. The sensitivity, specificity, Kappa value and the area of under ROC of each method and their combinations (parallel tests) were compared. RESULTS: The sensitivity of TS, Pap, TCT and HPV were 32.2%, 42.2%, 74.4% and 47.8%, with specificity of 96.7%, 93.7%, 78.8% and 84.8% in detecting cervical cancer, respectively. The sensitivity of the parallel tests, namely TCT/HPV, TCT/TS, Pap/TS and HPV/TS were 65.6%, 87.8%, 82.2% and 86.7%, with the specificity of 81.1%, 74.5%, 75.8% and 67.2%, respectively. In light of the areas of under ROC, significant differences were noted between the parallel tests of TS/Pap and TS/TCT (P<0.05), but not between TCT/Pap and TCT/TS (P>0.05); significant differences were found between the parallel tests with TS and those without TS (P<0.05), but not between TS alone and the parallel tests incorporating TS (P>0.05), nor between the 4 parallel tests (P>0.05). CONCLUSION: As a new modality for early screening of cervical carcinoma, TS offers a means for real-time cancer detection with better diagnostic efficacy than Pap and HPV and equivalent efficacy to TCT. The combination of TS and cytological tests can further enhance the diagnostic accuracy.
Subject(s)
Early Detection of Cancer/methods , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology , Adolescent , Adult , Aged , Cytodiagnosis , Female , Humans , Middle Aged , Sensitivity and Specificity , Vaginal Smears , Young AdultABSTRACT
OBJECTIVE: To evaluate long term effect and related factors in patients with menorrhagia treated by microwave endometrial ablation (MEA). METHODS: Total of 334 women with menorrhagia were treated by MEA, the range of age was from 29 to 59 years old. Among them, 59 cases were complicated by adenomyosis. All the patients were followed up on the change of menstrual cycle, the amount of flow, improvement of anaemia and complication. Fifty-three women underwent outpatient diagnostic hysteroscopy, the biopsy tissue was taken from the endometrium for histopathological examination. The mean duration of follow-up was 64.7 months (3 - 96 months). RESULTS: The overall curative rate was 91.3% (305/334), of which amenorrhea rate was 49.7% (166/334), menstruation reduction rate was 41.6% (139/334) ; 71.1% (140/197) of the cases who previously had dysmenorrhea had relieved their pelvic pain and the satisfactory rate was 91.9% (307/334). Among patients > 40 years, 92.9% (196/211) of operation effective rate, 93.8% (198/211) of satisfactory rate and 64.9% (137/211) of amenorrhea rate were obtained, while patients
