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Aberrant upregulation and oncogenic roles of UBE2T are revealed in several cancers. However, the expression, clinical significance, and functions of UBE2T have not been explored in ovarian cancer (OC). In this study, the expression of UBE2T and its relation with clinicopathological features and prognosis of OC patients were explored by analyzing online data and experimental data. Besides, the functions of UBE2T in OC cells were investigated by in vitro experiments, including CCK-8, plate clone formation, and Transwell assays. Finally, the underlying mechanism of UBE2T associated functions in OC was analyzed. The results indicated that UBE2T was significantly upregulated in OC tissues. UBE2T expression was notably correlated with clinical features, such as primary T stage and FIGO stage in OC patients. UBE2T, acting as an independent prognostic indicator, was inversely associated with the prognosis of OC patients. The UBE2T knockdown remarkably suppressed the growth, proliferation, and invasion of OC cells, indicated by impaired cell viability, fewer cell clones, and invasive cells. Mechanistically, UBE2T depletion suppressed epithelial-mesenchymal transition (EMT), which was caused by autophagy activation due to inactivation of AKT/mTOR in OC cells with UBE2T knockdown. Collectively, our findings confirm that UBE2T upregulation predicts poor prognosis and promotes malignant progression in OC. UBE2T upregulation suppresses autophagy and subsequently boosts EMT via activating the AKT/mTOR axis, which accounts for the underlying mechanism of oncogenic roles of UBE2T in OC.

The expressions and roles of protein inhibitor of activated STAT (PIAS) proteins, a group of proteins with STAT inhibition and SUMOylation E3 ligase activity, are rarely revealed in endometrial cancer (EC). In this study, we analyzed the expressions of PIASs and their relationships with clinical features by mining online data through web servers, including UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) in EC. The expressions of PIASs in EC tissues were further validated by immunohistochemistry (IHC). The online analyses revealed only PIAS1 was consistently downregulated both at mRNA and protein level in EC, which was validated by the IHC. Subsequently, the mechanism of PIAS1 downregulation was explored with online tools like UALCAN, cBioPortal, LinkedOmics, and the Encyclopedia of RNA Interactomes (ENCORI). The results indicated that the mutation rate of PIAS1 was extremely low and not associated with PIAS1 expression. The promoter methylation level of PIAS1 was comparable between normal and EC tissues. miR-182-5p and miR-96-5p with negative association with PIAS1 in EC were predicted to target PIAS1. Dual luciferase reporter assay confirmed miR-182-5p and miR-96-5p could target PIAS1 in EC. MiR-182-5p and miR-96-5p inhibitors could upregulate PIAS1 in EC cells. Moreover, ectopic PIAS1 expression and STAT3 inhibitor treatment significantly inhibited STAT3's activity and the levels of miR-182-5p and miR-96-5p in EC cells. Collectively, our findings revealed PIAS1 was downregulated in EC, which was caused by upregulation of miR-182-5p and miR-96-5p, and PIAS1 downregulation further activated STAT3 and increased the expression of miR-182-5p and miR-96-5p, confirming miR-182-5p and miR-96-5p mediated the negative feedback regulatory loop between PIAS1 and STAT3 in EC.

The reason for the formation of an anhydrous and surfactant-free deep eutectic solvent (DES)-based microemulsion system has been widely explored so far. Dissipative dynamism (DPD) is used to simula...

Aim: To investigate exosomal RNAs (long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs)) profiling and their related networks in endometriosis (EMs). Materials & methods: RNA sequence was performed in exosomes from ovarian endometriomas (EC), eutopic endometria (EU) and normal endometria (Control) stromal cells. The bioinformatics algorithms evaluated competing endogenous RNA (ceRNA) networks. The top-ranked ceRNA networks were confirmed by RT-PCR. Results: Overlapped differentially expressed 938 lncRNAs, 39 miRNAs and 1449 mRNAs were identified. 13 co-expression modules and 61 ceRNA networks were constructed. Conclusion: This study for the first time shows exosomal RNA biomarkers and lncRNA-related networks in EMs, which reveals a novel molecular mechanism of EMs and provides new resources for EM diagnosis and treatment.

PurposeRecent studies have demonstrated the differential expression of micro(mi)RNAs in endometriosis. Previously, we reported the low expression of miR-141 in patients with this disease. Epithelial-to-mesenchymal transition (EMT) and the transforming growth factor-beta1 (TGF-β1)-induced SMAD2 signalling pathway are central to tumour proliferation and invasion. However, the role of miR-141 in regulating the TGF-β1/SMAD2 signalling pathway and the associated EMT to be elucidated.MethodsThe levels of TGF-β1/SMAD2 signalling and EMT markers expression in eutopic and ectopic endometria of endometriosis were determined by immunohistochemistry and western blot analyses. MiR-141 expression was analysed by quantitative reverse-transcription polymerase chain reaction. Cellular invasion and proliferation were determined by transwell and CCK-8 assays, respectively. Functional assay of miR-141 was performed using plasmid and shRNA transfection methods.ResultThe presence of miR-141, EMT, and TGF-β1/SMAD2 signalling markers were detected in eutopic and ectopic endometria of endometriosis. TGF-β1-induced EMT in Ishikawa (ISK) cells by activating the SMAD2 signalling pathway, whereas miR-141 inhibited the TGF-β1-induced EMT, proliferation and invasion abilities of these cells.ConclusionThese data identify miR-141 as a novel driver of EMT in endometriosis, implicates the link between miR-141 and TGF-β1/SMAD2 signalling pathway in the context of endometriosis, and underscore the role of EMT in the development of endometriosis.

Globally, cervical cancer (CC) is the most common malignant tumor of the female reproductive system and its incidence is only second after breast cancer. Although screening and advanced treatment strategies have improved the rates of survival, some patients with CC still die due to metastasis and drug resistance. It is considered that cancer is driven by somatic mutations, such as single nucleotide, small insertions/deletions, copy number, and structural variations, as well as epigenetic changes. Previous studies have shown that cervical intraepithelial neoplasia is associated with copy number variants (CNVs) and/or mutations in cancer-related genes. Further, CC is also related to genetic mutations. The present study analyzed the data on somatic mutations of cervical squamous cell carcinoma (CESC) in the Cancer Genome Atlas database. It was evident that the Apolipoprotein B mRNA editing enzyme-catalyzed polypeptide-like (

Endometriosis (EMs) is a benign gynecological disorder showing some tumor-like migratory and invasive phenotypes. This study intended to investigate the role of microRNA-30c (miR-30c) in EMs, which is involved with B-cell lymphoma 9 (BCL9), an activator of the Wnt/β-catenin signaling pathway. EMs specimens were clinically collected for determination of miR-30c and BCL9 expression. Exosomes were isolated from endometrial epithelial cells (EECs), and the uptake of exosomes by ectopic EECs (ecto-EECs) was characterized using fluorescence staining and confocal microscopy. The binding of miR-30c to BCL9 was validated by dual-luciferase reporter assay. Artificial modulation (up- and down-regulation) of the miR-30c/BCL9/Wnt/CD44 regulatory cascade was performed to evaluate its effect on ecto-EEC invasion and migration, as detected by Transwell and wound healing assays. A mouse model of EMs was further established for in vivo substantiation. Reduced miR-30c expression and elevated BCL9 expression was revealed in EMs ectopic tissues and ecto-EECs. Normal EECs-derived exosomes delivered miR-30c to ecto-EECs to suppress their invasive and migratory potentials. Then, miR-30c was observed to inhibit biological behaviors of ecto-EECs by targeting BCL9, and the miR-30c-induced inhibitory effect was reversed by BCL9 overexpression. Further, miR-30c diminished the invasion and migration of ecto-EECs by blocking the BCL9/Wnt/CD44 axis. Moreover, miR-30c-loaded exosomes attenuated the metastasis of ecto-EEC ectopic nodules. miR-30c delivered by EECs-derived exosomes repressed BCL9 expression to block the Wnt/β-catenin signaling pathway, thus attenuating the tumor-like behaviors of ecto-EECs in EMs.

Background: To evaluate the effect of the uncertainty training on improvement of students’ diagnostic ability. Methods: Data were collected on 70 fifth year medical students enrolled in the Case Discussion courses on Obstetrics and Gynecology in the spring of 2020. Of these students, 36 were in the uncertainty training group and 34 in the control group. The effect of training was evaluated by cognitively diagnostic assessment which mapped exam questions to 4 attributes assessing clinical reasoning and basic science knowledge. Results: Uncertainty training was able to improve students’ ability to use basic science concepts for inference and problem solving, and the ability to integrate complex clinical information to arrive at a diagnosis. But it could not improve students’ ability on the basic recall of foundational concepts and the ability to use basic science concepts in clinical reasoning. Medical students could do well in integrating complex clinical information although they didn’t recall basic science knowledge well. Conclusions: Uncertainty training could be used as an effective teaching method in Case Discussion course on Obstetrics and Gynecology. However, students still need to improve their basic knowledge besides the training.

BACKGROUND We aimed this investigation to screen and analyze the risk factors of postoperative lymphatic leakage of gynecological malignant tumors that contribute to the treatment of the diseases. MATERIAL AND METHODS According to the occurrence of lymphatic leakage after an operation, 655 patients with pelvic lymph node and/or abdominal para-aortic lymph node dissection for gynecological malignant tumor were retrospectively analyzed and divided into a case group and a control group. Univariate and multivariate logistic regression analysis were used to screen the effective independent risk factors and establish a clinical prediction model. The differentiation and calibration of the clinical prediction model were evaluated, and we performed internal and external validation of the model with 207 cases. RESULTS The surgeons, the number of removed lymph nodes, the field and range of lymph nodes to be removed, the method of drainage, and postoperative infection are the independent risk factors of lymphatic leakage after lymph node dissection for gynecological malignant tumors. The area under the ROC curve of the clinical prediction model was 0.839 (P

Endometriosis is a common gynecologic disorder with enigmatic etiopathogenesis and is characterized by tumor-like biological behaviors. Epithelial-mesenchymal transition (EMT) has been recognized as a core mechanism of endometriosis. Recently, circular RNAs (circRNAs) have attracted considerable attention because they play an important role in the progression of cancer. However, little is known about the function of circRNAs in endometriosis. This study is intended to investigate the involvement of circRNAs and microRNAs in the process of EMT in ovarian endometriosis in vitro. We found that relative RNA levels of hsa_circ_0067301 and miR-141–5p were significantly reduced in ectopic endometrium when compared to control endometrium. Hsa_circ_0067301 knockdown could promote the proliferation and migration in Ishikawa and End1/E6E7 cells, concomitant with increased the relative protein expression against Notch-1, Hes-1, N-cadherin, and vimentin but reduced expression of E-cadherin. After co-transfection with the miR-141–5p inhibitor, the miR-141–5p that competes for binding to hsa_circ_0067301 was reduced, reversed EMT and partially restored the expression of Notch-1 and Hes-1. Results demonstrate the hsa_circ_0067301/miR-141–5p/Notch-1 axis plays an important regulatory role in the process of EMT in endometriosis. The study highlighted the importance of circRNAs in ovarian endometriosis and provided unique insights into the molecular basis concerning the pathogenesis of endometriosis.

To construct a lentiviral vector with endostatin (ES) and staphylococcal enterotoxin CBy inserting ES and SEC3 gene into the plasmid and then transfect 293 T cell, the co-expressed (SEC3-ES) vector were constructed. A series of experiments in vitro were carried out to detect its anti-tumor capacity.SEC3 expression of the vector is about 3 times of GV365-SEC3 vector, and ES expression is over 22.5-fold compared with GV365-ES vector. Moreover, OD490 value of CO group (1.212 ± 0.003) was notably lower than NC (negative control) group (1.124 ± 0.01) (P 0.05) in MTT assay. Cell cycle analysis showed it could block Hela cells in S phase. Meanwhile, in wound healing assay, cells of CO group migrated at a slower rate (0.59 ± 0.02) compared with NC group (0.65 ± 0.02)(P 0.01).The successful construction of co-expressed vector lays the foundation for further studies in vivo. These promising results suggest a new strategy to treating cervical cancer.

Cervical cancer (CC) is the second most common malignancy in females. Owing to poor diagnosis, resistance to the systemic therapies, and high recurrence rate, patients with CC have a relatively poor prognosis. The role of a signaling pathway in CC has always been the focus among worldwide researchers. As reported before, aberrant expression of proteins associated with signaling pathways, such as phosphatidylinositol 3-kinase(PI3K), EGF-R, β-catenin, and Erk and Bcl-2 was discovered in CC. Therefore, aberrant molecular signaling pathways are significant parts of cervical carcinogenesis. Recently discovered long noncoding RNAs (lncRNAs) as a new regulator player of molecular biology in CC have always been reported. In this review, we highlighted the role of lncRNA in signaling pathway implicated in CC and outlined the molecular mechanism of lncRNA in it. All of these present an opportunity for developing diagnosis and therapies against CC.

The expressions and roles of protein inhibitor of activated STAT (PIAS) proteins, a group of proteins with STAT inhibition and SUMOylation E3 ligase activity, are rarely revealed in endometrial cancer (EC). In this study, we analyzed the expressions of PIASs and their relationships with clinical features by mining online data through web servers, including UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) in EC. The expressions of PIASs in EC tissues were further validated by immunohistochemistry (IHC). The online analyses revealed only PIAS1 was consistently downregulated both at mRNA and protein level in EC, which was validated by the IHC. Subsequently, the mechanism of PIAS1 downregulation was explored with online tools like UALCAN, cBioPortal, LinkedOmics, and the Encyclopedia of RNA Interactomes (ENCORI). The results indicated that the mutation rate of PIAS1 was extremely low and not associated with PIAS1 expression. The promoter methylation level of PIAS1 was comparable between normal and EC tissues. miR-182-5p and miR-96-5p with negative association with PIAS1 in EC were predicted to target PIAS1. Dual luciferase reporter assay confirmed miR-182-5p and miR-96-5p could target PIAS1 in EC. MiR-182-5p and miR-96-5p inhibitors could upregulate PIAS1 in EC cells. Moreover, ectopic PIAS1 expression and STAT3 inhibitor treatment significantly inhibited STAT3's activity and the levels of miR-182-5p and miR-96-5p in EC cells. Collectively, our findings revealed PIAS1 was downregulated in EC, which was caused by upregulation of miR-182-5p and miR-96-5p, and PIAS1 downregulation further activated STAT3 and increased the expression of miR-182-5p and miR-96-5p, confirming miR-182-5p and miR-96-5p mediated the negative feedback regulatory loop between PIAS1 and STAT3 in EC.

Background: Endometriosis is a common gynecological disorder with high rates of infertility and pelvic pain. However, its pathogenesis and diagnostic biomarkers remain unclear. This study aimed to elucidate potential hub genes and key pathways associated with endometriosis in ectopic endometrium (EC) and eutopic endometrium (EU). Material and Method: EU and EC-associated microarray datasets were obtained from the gene expression omnibus (GEO) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene set enrichment analysis were performed to obtain further biological insight into the EU and EC-associated genes. Weighted gene co-expression network analysis (WGCNA) was performed to find clinically significant modules of highly-correlated genes. The hub genes that belong to both weighted gene co-expression network and protein-protein interaction (PPI) network were identified using Venn diagram. Results: We obtained EC and EU-associated microarray datasets GSE7305 and GSE120103. Genes in EC were mainly enriched in the immune response and immune cell trafficking, and genes in EU were mainly enriched in stress response and steroid hormone biosynthesis. PPI networks and weighted gene co-expression networks were constructed. EC-associated blue module, EU-associated magenta module and their function annotations were identified. 12 hub genes in EC and 16 hub genes in EU were recognized and further validated. Conclusion: Our study identified for the first time the hub genes and enrichment pathways in the EC and EU using WGCNA, which may provide a comprehensive understanding of the pathogenesis of endometriosis and have important clinical implications for the treatment and diagnosis of endometriosis. Funding: This work was supported by the National Natural Science Foundation of China [grant number 81671437, 81771558], Natural Science Foundation of Hunan Province [grant number 2020JJ4814], the Fundamental Research Funds for the Central Universities 287 of Central South University [grant number 2020zzts285]. Declaration of Interest: None to declare.

Novel biomarkers are needed to accelerate the diagnosis and treatment of endometriosis. We performed RNA sequencing to explore the expression profiles of exosomal circular RNAs (circRNAs), microRNAs (miRNAs) and mRNAs in patients with ovarian endometriomas, eutopic endometria and normal endometria. Differentially expressed genes between the different pairs of groups were analyzed and functionally annotated. Then, miRNA-target RNA pairs were identified, competing endogenous RNA (ceRNA) scores were calculated, gene expression characteristics were determined, and these parameters were used to construct an exosomal ceRNA network. We identified 36 candidate hub genes with high degrees of gene connectivity. We also topologically analyzed the ceRNA network to obtain a hub ceRNA network of circRNAs with the highest closeness and ceRNA efficiency. Twelve genes overlapped between the 36 candidate hub genes and the genes in the hub ceRNA network. These 12 genes were considered to be exosomal RNA-based biomarkers, and circ_0026129/miRNA-15a-5p/ATPase H+ transporting V1 subunit A (ATP6V1A) were at the center of the ceRNA network. By determining the exosomal RNA expression profiles of endometriosis patients and constructing a circRNA-associated ceRNA network, these findings provide insight into the molecular pathways of endometriosis and new resources for its diagnosis and treatment.

Endometrial cancer is one of the three major malignant tumors of the female reproductive system. Although cyclin-dependent kinase 9 (CDK9) has a definitive pathogenic role in various types of cancer, little is known concerning its function in endometrial cancer. Our study was conducted to evaluate the expression and therapeutic potential of CDK9 in endometrial cancer. CDK9 expression was determined by immunohistochemistry in endometrial cancer tissues constructed with paired primary, metastatic, and recurrent tumor tissues from 32 endometrial cancer patients. Small interfering RNA (siRNA) and inhibitors of CDK9 were used to evaluate the effect of CDK9 inhibition on the anti-apoptotic activity and proliferation in endometrial cancer cells. Colony formation assay and wound-healing assays were adopted to assess clonal formation and migratory capacity. The results of the immunohistochemistry demonstrated that CDK9 was highly expressed in the human endometrial cancer cell lines; moreover, it was elevated in metastatic and recurrent endometrial tumor tissue compared when compared with that in patient-matched primary endometrial tumor tissue. Knockdown of CDK9 with siRNA and inhibition of CDK9 activity with the inhibitor suppressed cell proliferation and promoted apoptosis in endometrial cancer. In conclusion, our results provide evidence that CDK9 may be a potential prognostic biomarker and a promising therapeutic target for the treatment of endometrial cancer in the future.

Background Endometriosis (EMs) is a non-malignant gynecological disease, whose pathogenesis remains to be clarified. Recent studies have found that hypoxia induces epithelial-mesenchymal transition (EMT) as well as epigenetic modification in EMs. However, the relationship between EMT and demethylation modification under hypoxia status in EMs remains unknown. Methods The expression of N-cadherin, E-cadherin and TET1 in normal endometria, eutopic endometria and ovarian endometriomas was assessed by immunohistochemistry and immunofluorescence double staining. 5-hmC was detected by fluorescence-based ELISA kit using a specific 5-hmC antibody. Overexpression and inhibition of TET1 or hypoxia-inducible factor 2α (HIF-2α) were performed by plasmid and siRNA transfection. The expression of HIF-2α, TET1 and EMT markers in Ishikawa (ISK) cells (widely used as endometrial epithelial cells) was evaluated by western blotting. The interaction of HIF-2α and TET1 was analyzed by chromatin immunoprecipitation. Results Demethylation enzyme TET1 (ten-eleven translocation1) was elevated in glandular epithelium of ovarian endometrioma, along with the activation of EMT (increased expression of N-cadherin, and decreased expression of E-cadherin) and global increase of epigenetic modification marker 5-hmC(5-hydroxymethylcytosine). Besides, endometriosis lesions had more TET1 and N-cadherin co-localized cells. Further study showed that ISK cells exhibited enhanced EMT, and increased expression of TET1 and HIF-2α under hypoxic condition. Hypoxia-induced EMT was partly regulated by TET1 and HIF-2α. HIF-2α inhibition mitigated TET1 expression changes provoked by hypoxia. Conclusions Hypoxia induces the expression of TET1 regulated by HIF-2α, thus may promote EMT in endometriosis.

Background: Aberrant upregulation and oncogenic roles of UBE2T have been revealed in several cancers. However, the expression, clinical significance, and functions of UBE2T has not been explored in ovarian cancer (OC).Methods: In this study, the mRNA and protein expression of UBE2T in OC were detected via analyzing the online databases and immunohistochemical staining. Moreover, relations of UBE2T expression with clincopathological features and prognosis OC patients were further analyzed. Besides, the effects of UBE2T knockdown on growth, proliferation, and invasion of OC cells were investigated by CCK-8, plate clone formation, and Transwell assays. Finally, the underlying mechanism of UBE2T associated functions in OC was analyzed.Results: The results indicated that UBE2T was significantly upregulated in OC tissues. UBE2T expression was notably correlated with clinical features such as primary T stage, TNM stage in OC patients. UBE2T, acting as an independent prognostic indicator, was inversely associated with prognosis of OC patients. UBE2T knockdown remarkably suppressed the growth, proliferation, and invasion of OC cells indicating by impaired cell viability, less cell clones and invasive cells. Mechanistically, the oncogenic roles of UBE2T was exerted by inhibiting autophagy via maintaining AKT/mTOR activity in OC.Conclusion: Collectively, our findings confirm UBE2T upregulation predicts poor prognosis and promotes malignant progression via suppressing autophagy in OC, suggesting the promising values of UBE2T both in diagnosis and treatment of OC.

Discovery of genes and molecular mechanism involved in cervical cancer development would promote the prevention and treatment. By comparing gene expression profiles of cervical carcinoma in situ (CCIS) and adjacent normal tissues, we identified a potential cancer-promoting gene, IMPA2. This study aimed to elucidate the role of IMPA2 and underlying molecular mechanisms in cervical cancer progression. To do this expression of IMPA2 was compared between human cervical cancer and corresponding adjacent normal cervical tissues firstly. CCK-8 assay, clone formation assay, wound healing assay, transwell assay, and tumor formation in nude mice were performed to demonstrate the effect of IMPA2 in cervical cancer proliferation and metastasis. Further proteomic profiling and western blotting explored the molecular pathway involved in the IMPA2-regulating process. The results showed that IMPA2 gene expression was upregulated in cervical cancer. Consistently, silencing of IMPA2 suppressed tumor formation in BALB/c nude mice. Short hairpin RNA (shRNA)-mediated IMPA2 silencing significantly inhibited proliferation and colony-forming abilities of cervical cancer cells, while IMPA2 overexpression had little impact. Also, IMPA2 silencing suppressed cellular migration, but overexpression promoted migration. Proteomics analysis revealed the involvement of mitogen-activated protein kinase (MAPK) pathway in tumor-promoting action of IMPA2. Significantly, the inhibition of IMPA2 activated ERK phosphorylation, and its inhibitory effects can be restored by using selective ERK inhibitor, FR180204. In conclusion, IMPA2 acts as an oncogene in the proliferation and migration of cervical cancer. IMPA2 downregulated ERK phosphorylation to promote cervical cancer. These findings identify a new mechanism underlying cervical cancer and suggest a regulating effect of IMPA2 in MAPK signaling pathway.

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Cervical cancer (CC) is the second most common malignant cancer in women. CC is difficult to diagnose, has a high recurrence rate, and is resistant to systemic therapies; as a result, CC patients have a relatively poor prognosis. One potential link to CC is the Wnt signaling pathway and its downstream effectors, which regulate cell differentiation, proliferation, migration, and fate. The aberrant activation of Wnt signaling is associated with various cancers, including CC. Recent studies have shown that activating or inhibiting the intracellular signal transduction in this pathway can regulate cancer cell growth and viability. This review will summarize the experimental evidence supporting the significance of the Wnt signaling pathway in CC, and will also discuss the current clinical role of Wnt signaling in CC diagnosis, therapy, and prognosis.