Resveratrol protected against the development of endometriosis by promoting ferroptosis through miR-21-3p/p53/SLC7A11 signaling pathway.

Resveratrol is involved in regulating ferroptosis, but its role in Endometriosis (EMS) is not clear. In this study, we aim to investigate the effect of ferroptosis and resveratrol intervention in the pathogenesis of EMS cyst. Cell proliferation, migration, and oxidative stress level were analyzed. The interaction of miR-21-3p and p53 was analyzed by dual luciferase assay. The interaction between p53 and SLC7A11 were analyzed by chromatin immunoprecipitation (CHIP). The miR-21-3p, GPX4, ACSL4, FTH1, p53, SLC7A11, Ptgs2 and Chac1 expression were analyzed by RT-qPCR or Western blot. The Fe3+ deposition and miR-21-3p, GPX4, FTH1 and SLC7A11 expressions were increased, and ACSL4, p53, Ptgs2 and Chac1 expression were decreased in EMS patients. Resveratrol inhibited migration, induced Ptgs2 and Chac1 expression in EESCs. Overexpression of miR-21-3p inhibited p53, Ptgs2 and Chac1 expression, and promoted SLC7A11 expression, which was reversed by resveratrol. miR-21-3p bound to p53, which interacted with SLC7A11. Resveratrol promoted Ptgs2 and Chac1 expression in the sh-p53 EESCs. Resveratrol reduced miR-21-3p and SLC7A11 expressions, and increased p53, Ptgs2 and Chac1 expressions, and Fe3+ deposition in the lesion tissues of EMS mice, which were reversed by miR-21-3p mimics. Resveratrol activated p53/SLC7A11 pathway by down-regulating miR-21-3p to promote ferroptosis and prevent the development of EMS.

Novel Diagnostic Biomarker BST2 Identified by Integrated Transcriptomics Promotes the Development of Endometriosis via the TNF-α/NF-κB Signaling Pathway.

Endometriosis (EMS) is a common gynecological condition with apparent heterogeneity, lack of diagnostic markers, and unclear pathogenesis. A series of bioinformatics methods were employed to explore EMS's pathological mechanisms and potential biomarkers by analyzing the combined datasets of EMS (GSE7305, GSE7307, GSE58198, E-MTAB-694), which included 34 normal, 127 eutopic, and 46 ectopic endometrium samples. Then, wet-laboratory experiments (including Western blot, qRT-PCR, and Immunohistochemistry, Immunofluorescence, CCK-8, EdU, Wound healing, Transwell, and Adhesion assays) were applied to examine the biomarkers' expression and function in primary endometrial stromal cells. Bioinformatic analysis indicated that the core pathogenesis of EMS was dysregulated immune-inflammation and tissue remolding processes. Among the upregulated DEGs, BST2 was screened as a potential diagnostic biomarker in EMS, which associated with the revised American Fertility Society (r-AFS) stage and immune-inflammation processes of EMS. Moreover, BST2's overexpression was affirmed in the RNA and protein levels in EMS tissues. In vitro experiments demonstrated that TNF-α promoted the expression of BST2 in ESCs. And BST2 knockdown inhibited migration, invasion, adhesion, and inflammation except for the proliferation of ESCs, probably via the TNF-α/NF-κB pathway. Through a combination of wet and dry studies, we concluded that the core pathogenesis of endometriosis was dysregulated immune-inflammation and tissue remolding, and BST2 might be a potential diagnostic and therapeutic target in endometriosis.

Identification of Key Genes and Pathways associated with Endometriosis by Weighted Gene Co-expression Network Analysis.

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: EC and EU-associated microarray datasets were obtained from the gene expression omnibus (GEO) database. Gene set enrichment analysis was 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 the weighted gene co-expression network and protein-protein interaction (PPI) network were identified using a Venn diagram. Results: We obtained EC and EU-associated microarray datasets GSE7305 and GSE120103. Genes in the EC were mainly enriched in the immune response and immune cell trafficking, and genes in the EU were mainly enriched in stress response and steroid hormone biosynthesis. PPI networks and weighted gene co-expression networks were constructed. An EC-associated blue module and an EU-associated magenta module were identified, and their function annotations revealed that hormone receptor signaling or inflammatory microenvironments may promote EU passing through the oviducts and migrating to the ovarian surfaces, and adhesion and immune correlated genes may induce the successful ectopic implantation of the endometrium (EC). Twelve hub genes in the EC and sixteen hub genes in the EU were recognized and further validated in independent datasets. 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.

Independent Risk Factors of Postoperative Lymphatic Leakage in Patients with Gynecological Malignant Tumor: A Single-Center Retrospective Study.

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<0.001), the calibration Hosmer-Lemeshow test shows χ²=4.381, P=0.821. Through 10-fold cross-validation, the average correct rate of the prediction model was 0.899, the area under the ROC curve of the external verification group was 0.741, and the calibration Hosmer-Lemeshow test showed χ²=12.728, P=0.122. CONCLUSIONS The new logistic prediction model showed a good degree of differentiation and calibration in both the modeling and verification groups, and it can be used for early warning of the occurrence of lymphatic leakage after lymph node dissection.

microRNA-141 inhibits TGF-ß1-induced epithelial-to-mesenchymal transition through inhibition of the TGF-ß1/SMAD2 signalling pathway in endometriosis.

PURPOSE: Recent 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-ß1)-induced SMAD2 signalling pathway are central to tumour proliferation and invasion. However, the role of miR-141 in regulating the TGF-ß1/SMAD2 signalling pathway and the associated EMT to be elucidated. METHODS: The levels of TGF-ß1/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. RESULT: The presence of miR-141, EMT, and TGF-ß1/SMAD2 signalling markers were detected in eutopic and ectopic endometria of endometriosis. TGF-ß1-induced EMT in Ishikawa (ISK) cells by activating the SMAD2 signalling pathway, whereas miR-141 inhibited the TGF-ß1-induced EMT, proliferation and invasion abilities of these cells. CONCLUSION: These data identify miR-141 as a novel driver of EMT in endometriosis, implicates the link between miR-141 and TGF-ß1/SMAD2 signalling pathway in the context of endometriosis, and underscore the role of EMT in the development of endometriosis.

The role of lncRNAs in signaling pathway implicated in CC.

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, ß-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.

Downregulated circular RNA hsa_circ_0067301 regulates epithelial-mesenchymal transition in endometriosis via the miR-141/Notch signaling pathway.

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.

Eutopic endometrium from patients with endometriosis modulates the expression of CD36 and SIRP-α in peritoneal macrophages.

AIM: This study aimed to investigate the in vitro alterations of the expression of signal regulatory protein-α (SIRP-α) and CD36 in macrophages in the endometriosis condition. METHODS: The expression of SIRP-α and CD36 was measured in peritoneal macrophages and peripheral blood mononuclear cells of endometriosis patients and control participants. The expressions of SIRP-α and CD36 were measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with interleukin-6 (IL-6)-induced conditioned medium, eutopic versus normal endometrial homogenate, or lipopolysaccharide in the presence or absence of nuclear factor kappa-B (NF-κB) or transforming growth factor (TGF-ß) inhibitors, respectively. RESULTS: Peritoneal macrophages that were isolated from women with endometriosis exhibited an enhanced expression of SIRP-α and a decreased expression of CD36 compared to control participants. Women with endometriosis had significantly higher levels of SIRP-α and CD36 in peripheral circulating mononuclear cells than in control participants. SIRP-α expression was significantly increased, whereas the CD36 expression was decreased in THP-1 cell-derived macrophages after treatment with eutopic endometrial homogenate. Intervention with IL-6-induced conditioned medium resulted in the downregulation of SIRP-α but the upregulation of CD36 in THP-1 cells. Incubation with the NF-κBp50 inhibitor decreased the expression of CD36 and SIRP-α in macrophages that were treated with normal endometrial homogenate, whereas the TGF-ß inhibitor enhanced the CD36 expression of THP-1 cell-derived macrophages treated with eutopic endometrial homogenate. CONCLUSION: The eutopic endometrium could reduce the phagocytic ability of peritoneal macrophages in women with endometriosis through the modulation of SIRP-α and CD36 expression. Inhibition of the TGF-ß signal pathway may be a potential therapeutic target for the treatment of endometriosis.

[Research advances in TET enzyme and its intermediate product 5hmC].

DNA methylation is a significant epigenetic modification mode, which plays an important role in embryo reprogramming, stem cell differentiation and tumor occurrence. The ten-eleven translocation (TET) enzyme is a crucial demethylation enzyme, which can catalyze 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine(5caC). These bases represent the epigenetic modifications of DNA and regulate the process of DNA methylation. Understanding the role of TET enzyme in regulating the DNA methylation modification and gene expression can help us to gain the knowledge for the normal growth development and epigenetic regulation in human diseases.

[Effect of adipose-derived mesenchymal stem cell transplantation on cyclophosphamide-induced ovarian damage in rats].

OBJECTIVE: To explore the effect of adipose-derived mesenchymal stem cells (ADMSCs) on ovarian damage induced by cyclophosphamide (CTX) and its mechanism.
 Methods: ADMSCs isolated from adipose tissue of female SD rats were cultured and divided into a blank group and a CTX group (n=15 in each group). CTX (75 mg/kg) was injected intraperitoneally to establish a model of ovarian damage in rats. A total of 45 female SD rats were also divided into 3 groups: Group A (15 rats, only injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline), Group B [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 0.6 mL ADMSCs (6×105 cells) by the tail vein], and Group C [15 rats, injected intraperitoneally with 75 mg/kg CTX diluted with 1 mL 0.9% saline, after 4 estrus cycles, injected 40 mL ADMSCs (20 mL per side, 2×104 cells) in situ ovarian]. After 4 estrus cycles, the changes of quality of life, ponderal growth were recorded, the sex hormone levels [estradiol (E2), follicle-stimulating hormone (FSH)] were tested by ELISA, and the morphology of ovarian tissue and follicle count were observed by HE staining. The expression of BMP-15, Bcl-2 and Bax in ovarian tissues were tested by immunohistochemistry, real-time PCR or Western blotting. The apoptosis rate of follicular cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay.
 Results: After transplantation of ADMSCs, compared with the Group A, their quality of life of rats in the Group B and C was improved, and the ponderal growth was increased (both P<0.01). Compared with the Group A, the serum E2 levels in the Group B and the Group C were increased (P<0.01, P<0.05), and the FSH levels in the Group B and C were decreased (both P<0.01). The granular cell layer, the number of corpus lutein and the count of various grade follicles were significantly increased, and many new follicles and mature oocytes were observed in the Group B and C. Compared with Group A, the count of primitive follicles, sinusoidal follicles, pre-ovulation follicles and total follicles, and pre-sinusoidal follicles were dramatically increased in the Group B. The follicle at all levels count was increased in the Group C than that in the Group A (all P<0.01). Comparing with the Group A, the expressions of BMP-15 and Bcl-2 were increased (all P<0.01), the expressions of Bax was decreased (both P<0.01), and the apoptosis rates of follicular cells were decreased in the Group B and C (both P<0.01). However, there was no difference between the Group B and the Group C in the above indexes (all P>0.05).
 Conclusion: ADMSCs transplantation can effectively repair ovarian damage induced by CTX in rats, which may be achieved by inhibiting mitochondrial apoptosis of granulosa cells.

Expression Profile Analysis of Circular RNAs in Ovarian Endometriosis by Microarray and Bioinformatics.

BACKGROUND Endometriosis is a common gynecologic disorder with enigmatic etiopathogenesis and is characterized by tumor-like biological behaviors. Recently, circular RNAs (circRNAs) have attracted considerable attention because they exert very important functions in the progression of human cancers. However, little is known about the functions and molecular mechanism of circRNAs in endometriosis. MATERIAL AND METHODS A total of 20 patients with ovarian endometriosis and 4 normal endometrium from women free of endometriosis were included in this study. Ectopic endometrium tissues and paired eutopic endometrium tissues were collected from ovarian endometriosis patients. We assessed the expression profiles of circRNAs in endometriosis by microarray analysis. Expression of selected circRNAs in those tissues was detected by quantitative real-time PCR (qRT-PCR). Based on the target prediction, we constructed a circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network and elucidated circRNAs through Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. RESULTS We detected 2237 circRNAs, differentially expressed among 3 groups, and then found 8 circRNAs that may be involved in the epithelial-mesenchymal transition process. The qRT-PCR validation suggested that circ_103470 and circ_101102 matched the microarray results. The functional analysis revealed 17 pathways, such as the mTOR signaling pathway, the Hippo signaling pathway, and the HIF-1 signaling pathway, which may be associated with the pathogenesis and development of endometriosis. CONCLUSIONS In general, our results suggest that 2 downregulated circRNAs (circ_103470 and circ_101102) may regulated epithelial-mesenchymal transition in endometriosis via miR-141-5p, which may be a promising therapeutic target in the future.

Sphingosine-1-phosphate activates the AKT pathway to inhibit chemotherapy induced human granulosa cell apoptosis.

To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis. We found that S1P (10 mm) statistically significantly decreased granulosa cell apoptosis after cyclophosphamide (CTX) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with LY294002, PI3K inhibitor. CONCLUSIONS: Treatment with S1P can inhibit the CTX-induced granulosa cell apoptosis. The S1P protective effect is mediated by activating the PI3K/Akt pathway.

[Effect of IL-1ß or TNF-α-treated human decidual cells on balance between Th1 and Th2 or Th17 and Treg immunity].

OBJECTIVE: To investigate the effect of IL-1ß or TNF-α-treated human decidual cells on the balance between Th1 and Th2 or Th17 and Treg.
 Methods: Human decidual cells were isolated and treated with estrogen (E2) and progesterone (P) for 7 days and then with IL-1ß or TNF-α for 24 h. The culture medium was collected to prepare conditioned medium. The T cells isolated from human decidual tissue were cultured in presence of conditioned medium for 72 h. ELISA was used to detect concentration of IFN-γ, IL-2, IL-5, IL-17 IL-10, and TGF-1ß in supernatants and quantitative real-time PCR was used to detect the mRNA expression of IFN-γ, IL-17, IL-10, and TGF-1ß.
 Results: The levels of IFN-γ, IL-2 and IL-17 were significantly increased when T cells were cultured in the conditioned medium compared with the control group (E2+P), while the levels of IL-5, IL-10, and TGF-1ß were not significantly changed. The mRNA expressions of IFN-γ and IL-17 mRNA were significantly increased when T cells were cultured in the conditioned medium compared with the control group (E2+P), while the mRNA expression of IL-10 and TGF-1ß was not significantly different.
 Conclusion: Human decidual cells treated by IL-1ß or TNF-α can shift the balance of Th1 and Th2 or Th17 and Treg toward Th1 and Th17 immunity.

An ESRG-interacting protein, COXII, is involved in pro-apoptosis of human embryonic stem cells.

Human embryonic stem cells(hESC) posses very promising application perspective in clinical transplant therapies for their characteristics of self-renewal and pluripotency. So efforts focusing on the mechanisms of the two characteristics are extremely important. ESRG, first identified by our group, is a candidate stemness gene of hESC for its much higher expression level in hESC comparing to that in 7-day embryoid bodies(EBs). Here, the proteins interacted with ESRG and its functions in hESC were explored. Yeast two-hybrid (Y2H) screening system was adopted to explore the interacting proteins of ESRG. Then Co-IP was performed to confirm the interactions between candidate proteins and ESRG. At last, the functions of validated interacting protein were explored by RNA interference(RNAi) and Western blot(WB). There were no autonomous activation and toxicity in the Y2H system, which verified its availability. Four candidate proteins, AAMP, DDT, GNB2L1 and COXII, were discovered, and the interaction between ESRG and COXII was ultimately confirmed. The expression of COXII in hESC was suppressed by siRNA, and the inhibited mitochondrial apoptosis was observed in hESC with downregulated COXII expression. Our work first validated the interaction between ESRG and COXII, and demonstrated that COXII serves as a pro-apoptotic protein in hESC. The results implied that ESRG may play an important role in regulating the apoptosis of hESC by interacting with COXII, and thus contribute a lot to the maintenance of hESC characteristics.

The Effect of Uncertainty Training on the Improvement of Diagnostic Ability in Chinese Medical Students.

Objective: 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. Conclusion: 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.

[Effect of letrozole on endometrosis and apoptosis of ectopic endometrial cells in rats].

OBJECTIVE: To investigate the therapeutic mechanism of letrozole, the third-generation aromatase inhibitor, on endometriotic lesions in a rat model and its effect on the apoptosis of ectopic endometrial cells. METHODS: Endometriosis was induced by autotransplanting pieces of uterus onto the peritoneum in rats. The rats with successful ectopic implants were divided into 2 groups: A letrozole group (n=15) and a control group (n=15). The volume, appearance, and histopathology of ectopic implant were determined before and after the treatment. Expression of P450arom, COX-2, bcl-2, and bax in the ectopic implant was detected by immunohistochemistry and RT-PCR in the 2 groups. RESULTS: The volume of ectopic implant in the letrozole group was significantly reduced compared with the control group (P<0.05). The protein and mRNA levels of P450arom and COX-2 in the ectopic implant were significantly decreased in the letrozole group compared with the control group (P<0.05). There was a positive correlation between the expression of P450arom and the expression of COX-2 (r=0.943, P<0.001; r=0.913, P<0.001). The protein and mRNA expression of bcl-2 was significantly decreased (P<0.05), and the bax protein and mRNA expression was significantly increased (P<0.05) in the ectopic implant with an increased bax/bcl-2 ratio in the letrozole group compared with the control group (P<0.05). CONCLUSION: Letrozole can obviously reduce the size of ectopic implant through decreasing P450arom and COX-2 expression, suppressing the secretion of estrogen, inhibiting the proliferation, and inducing the apoptosis of ectopic implants.

Linc-ROR Promotes EMT by Targeting miR-204-5p/SMAD4 in Endometriosis.

Endometriosis (EMs) is a systemic and chronic disease with cancer-like feature, namely, distant implantation, which caused heavy healthy burden of nearly 200 million females. LncRNAs have been proved as new modulators in epithelial-mesenchymal transition (EMT) and EMs. Quantitative real-time PCR was conducted to measure the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (Linc-ROR), and miR-204-5p in ectopic endometrium (n = 25), eutopic endometrium (n = 20), and natural control endometrium (n = 22). Overexpression of Linc-ROR, knockdown or overexpression of miR-204-5p in End1/E6E7 and Ishikawa cells, was conducted to detect the function of Linc-ROR and miR-204-5p in EMs. Furthermore, luciferase reports were used to confirm the combination of Linc-ROR and miR-204-5p and the combination between miR-204-5p and SMAD4. Cell-Counting Kit-8, EdU assay, transwell assays, and Western blotting were used to detect the function of Linc-ROR and miR-204-5p in EMs cancer-like behaviors and EMT process. Linc-ROR was up-regulated in ectopic endometrium. Overexpressed Linc-ROR promotes cell proliferation, invasion, and EMT process. Linc-ROR regulated the EMT process, cellular proliferation, and invasion of EMs via binding to miR-204-5p. In addition, overexpression of Linc-ROR up-regulated SMAD4, a target protein of miR-204-5p, with which regulated EMT process and cancer-like behaviors in EMs together. Linc-ROR/miR-204-5p/SMAD4 axis plays a vital role in regulation EMT process in EMs, which might become a novel therapeutic targets and powerful biomarkers in EMs therapy.

Bioinformatic Analyzes of the Association Between Upregulated Expression of JUN Gene via APOBEC-Induced FLG Gene Mutation and Prognosis of Cervical Cancer.

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 (APOBEC)-related mutation of the FLG gene can upregulate the expression of the JUN gene and ultimately lead to poor prognosis for patients with CC. Therefore, the findings of the current study provide a new direction for future treatment of CC.

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion by promoting epithelial-mesenchymal transition via inhibiting autophagy in an AKT/mTOR dependent manner in ovarian cancer.

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.