Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3.

Introduction: Although LncRNA JPX has been linked to a number of malignancies, it is yet unknown how it relates to endometrial carcinoma (EC). Investigating the expression, functional activities, and underlying molecular processes of lncRNA JPX in EC was the goal of this work. Methods: RT-qPCR was used to examine the differences in lncRNA/microRNA (miRNA, miR)/mRNA expression between normal cervical and EC tissues or cells. Cell Counting Kit-8, flow cytometry, and transwell were used to evaluate the association between lncRNA JPX/miR-140-3p/phosphoinositide-3-kinase catalytic subunit α (PIK3CA) in Ishikawa and JEC cell lines. The impact of JPX on the downstream janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway was investigated using Western blot analysis. Results: When comparing EC tissues to nearby normal tissues, JPX expression is markedly increased in EC tissues, with greater expression in advanced-stage EC. Furthermore, compared to normal epithelial cells, EC cell lines have higher levels of JPX expression. In Ishikawa and JEC endometrial cancer cell lines, we used siRNA-mediated suppression of JPX to find lower cell viability, increased apoptosis, cell cycle arrest, and reduced migration and invasion. We next verified that miR-140-3p binds to downstream target cells to impede the transcription and translation of PIK3CA, which in turn prevents the growth of Ishikawa and JEC cells. JPX functions as a ceRNA to adsorb miR-140-3p. This procedure required controlling JAK2/STAT3, a downstream signal. Conclusion: JPX enhances the development of Ishikawa and JEC cells and activates downstream JAK2/STAT3 signal transduction via the miR-140-3p/PIK3CA axis, offering a possible therapeutic target for the treatment of EC.

Selective venous sampling in primary hyperparathyroidism caused by ectopic parathyroid gland: a case report and literature review.

BACKGROUND: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion's location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. CASE PRESENTATION: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient's symptoms disappeared and serum levels of PTH and calcium normalized. CONCLUSIONS: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

Relations Between Body Fat Mass and Insulin Resistance in Non-Obese Patients with Idiopathic Hypogonadotropic Hypogonadism and Normal Glucose Tolerance.

The purpose of this study was to investigate the relationship between body fat mass and insulin resistance in non-obese patients with idiopathic hypogonadotropic hypogonadism (IHH) and normal glucose tolerance. A total of 42 patients with IHH and normal glucose tolerance, and BMI lower than 28 kg/m2 were recruited. Patients were required to have a normal glucose tolerance test for inclusion in the study. Ten Healthy subjects were recruited as control group. Laboratory studies included fasting insulin, testosterone, and lipids. Waist circumference (WC), weight, and body fat mass were measured, and waist-to-hip ratio (WHR), body mass index (BMI), HOMA-IR, and logHOMA-B were calculated. Data were compared between groups, and linear regression was used to determine relations. Blood pressure, fasting glucose, BMI, WHR, and lipids were similar between the groups. Fasting insulin levels (15.61±7.66 mIU/l vs. 7.60±3.84 mIU/l), logHOMA-B (2.39±0.29 vs. 2.03±0.21), HOMA-IR (3.38±1.71 vs. 1.64±0.91), and body fat mass (30.49±9.46% vs. 21.11±4.31%) were significantly greater in the IHH group compared with those in control group (all p<0.05). Multivariable linear regression showed that in IHH patients body fat mass was an independent predictor of fasting insulin level (ß=0.71, p<0.01), logHOMA-B (ß=0.02, p<0.05), and HOMA-IR (ß=0.14, p<0.05). Body fat mass is an independent predictor of insulin resistance in non-obese IHH patients with normal glucose tolerance.

MicroRNA­199a/b­5p inhibits endometrial cancer cell metastasis and invasion by targeting FAM83B in the epithelial­to­mesenchymal transition signaling pathway.

Our previous study demonstrated the role of family with sequence similarity 83, member B (FAM83B) in endometrial cancer tumorigenesis and metastasis. FAM83B is involved in epithelial­to­mesenchymal transition (EMT). However, the regulatory network of EMT, which promotes endometrial cancer cell metastasis, involving microRNAs (miRNAs/miRs) and FAM83B, has not been elucidated. To investigate the potential mechanism underlying miR­199a/b­5p in endometrial cancer, the effect of miR­199a/b­5p and its targeted FAM83B gene on the biological behaviour of endometrial cancer cells was assessed. The Gene Expression Omnibus dataset analysis results revealed that the expression levels of 150 miRNAs in non­cancerous endometrial tissues were upregulated compared with those in endometrial cancer tissues. TargetScan predicted that the nucleotides 672­679 of FAM83B 3'­untranslated region (UTR) were the target sites of miR­199a/b­5p. The differentially expressed miRNAs were enriched in several Kyoto Encyclopedia of Genes and Genomes pathways. Reverse transcription­quantitative PCR analysis revealed that the expression levels of miR­199a/b­5p in the endometrial non­cancerous cell lines were significantly upregulated compared with those in the six endometrial cancer cell lines. miR­199a/b­5p inhibited the EMT signaling pathway by regulating the expression levels of E­cadherin, N­cadherin, Snail, α­smooth muscle actin, vimentin and Twist. This suggested that miR­199a/b­5p inhibited endometrial cancer cell proliferation and migration through the inhibition of the EMT signaling pathway. Furthermore, the nucleotides 672­679 of the FAM83B 3'­UTR were demonstrated to be the binding site of miR­199a/b­5p. These results suggested that miR­199a/b­5p inhibited endometrial cancer cell proliferation and metastasis by targeting the 3'­UTR of FAM83B, which is involved in the EMT signaling pathway.

Mid-upper arm circumference as a simple tool for identifying central obesity and insulin resistance in type 2 diabetes.

BACKGROUND: Our research aimed to explore the correlation between mid-upper arm circumference (MUAC) and central obesity and insulin resistance (IR) in Chinese subjects with type 2 diabetes. MATERIALS: A total of 103 participants (60 men) were recruited in our study. MUAC was measured around the mid-arm between the shoulder and elbow. Waist circumference (WC) was obtained as central obesity parameter, and the IR parameter of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) was calculated. The subjects were divided into three groups according to the tertiles cut-points of MUAC level. RESULTS: Body mass index (BMI), WC, the percentages of central obesity and HOMA-IR were significantly higher in the groups with higher MUAC than those in the group with lower MUAC (all P < 0.05). Pearson analysis showed that MUAC was correlated with BMI, WC, waist-to-hip ratio (WHR), logHOMA-IR, low density lipoprotein cholesterol (LDL-C), uric acid (UA) and high density lipoprotein cholesterol (HDL-C) in all subjects. Multivariate linear regression analysis revealed that MUAC was independently associated with logHOMA-IR (ß = 0.036, P<0.001) after adjusting for age, gender, WHR, UA, TG, LDL-C and HDL-C. Binary logistic regression analysis revealed that MUAC was an independent predictor of central obesity (OR: 2.129, 95%CI: 1.311-3.457, P = 0.002). Furthermore, MUAC≥30.9cm for male and ≥30.0cm for female were the optimal cutoff values for identifying central obesity. CONCLUSIONS: Our study indicated that among Chinese subjects with type 2 diabetes, MUAC is a simple and effective tool for the determination of central obesity and IR. Additionally, the larger MUAC is proved to be more associated with metabolic risk factors of higher UA and LDL-C and lowever HDL-C.

Up-regulation of microRNA-203 inhibits myocardial fibrosis and oxidative stress in mice with diabetic cardiomyopathy through the inhibition of PI3K/Akt signaling pathway via PIK3CA.

Diabetic cardiomyopathy (DCM) refers to the myocardial dysfunction in the absence of coronary artery disease and hypertension. Recently, the role of microRNAs (miRs) in gene expression regulation has attracted much more attention. Studies have shown that the PI3K/Akt signaling pathway is involved in the growth, metabolism and apoptosis of myocardial cells. Therefore, this study aimed to explore the regulatory role of miR-203 in myocardial fibrosis in mice with DCM via involvement of the PI3K/Akt signaling pathway. Firstly, mouse model of diabetes mellitus (DM) was established and injected with agomir, antagomir or IGF-1 (PI3K/Akt signaling pathway activator) for investigating the role of miR-203 in PIK3CA and the PI3K/Akt signaling pathway. PIK3CA was identified as a target gene of miR-203, and overexpressed miR-203 inhibited the activation of PI3K/Akt signaling pathway. The obtained results indicated that up-regulation of miR-203 reduced myocardial hypertrophy, myocardial fibrosis, myocardial apoptosis, and levels of PIK3CA, PI3K, Akt, CoI I, CoI III, ANP, MDA and ROS in the myocardial tissues, by which DM-induced cardiac dysfunction and pathological changes could be ameliorated. Collectively, our present study highlighted that overexpression of miR-203 may function as a cardioprotective regulator in DCM by targeting PIK3CA via inactivation of PI3K/Akt signaling pathway.

Knocking down FAM83B inhibits endometrial cancer cell proliferation and metastasis by silencing the PI3K/AKT/mTOR pathway.

Family with sequence similarity 83 member B (FAM83B) has been recently identified as an oncogene involved in the development of various human cancers. However, the role of FAM83B in endometrial cancer tumorigenesis and metastasis is unclear. In this study, we found that the expression of FAM83B was upregulated in endometrial cancer tissues and cell lines. FAM83B expression in endometrial cancer tissues was significantly higher than that in normal tissues and higher FAM83B expression was closely related to poorly survival rate according to TCGA analysis. Moreover, FAM83B expression was correlated with International Federation of Gynecology and Obstetrics (FIGO)stage and myometrial invasion but had no significant correlation with age or histological grade. FAM83B knockdown inhibited endometrial cancer cell proliferation, migration, and invasion arrested the cell cycle at the G1/S stage and promoted apoptosis. FAM83B knockdown also inhibited endometrial cancer growth and lung metastasis in vivo. FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Furthermore, activation of the PI3K/AKT/mTOR pathway reversed FAM83B knockdown-induced autophagy promotion and inhibition of proliferation, migration, and invasion in endometrial cancer cells. Taken together, these results indicate that FAM83B promotes endometrial cancer cell proliferation and metastasis by inhibiting autophagy via activating the PI3K/AKT/mTOR pathway.

Cystatin C Is an Important Biomarker for Cardiovascular Autonomic Dysfunction in Chinese Type 2 Diabetic Patients.

BACKGROUND: Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. METHODS: A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 µmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. RESULTS: The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P < 0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r = -0.31, P < 0.001), SDANN (r = -0.25, P = 0.002), and logLF (r = -0.18, P = 0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (ß = -24.11, P = 0.015) and SDANN (ß = -19.88, P = 0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. CONCLUSIONS: Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.

A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways.

In this study we investigated the potential effects of a polysaccharide (HDP) from Hedyotis diffusa on the metastasis in human lung adenocarcinoma A549 cells. HDP (25, 50 and 100µg/ml) significantly suppressed the cell adhesion, invasion and migration of A549 cells in a dose dependent manner by downregulation of matrix metalloproteinase (MMP-2 and MMP-9) and upregulation of tissue inhibitors of metalloproteinase (TIMP-2 and TIMP-9). Moreover, HDP effectively downregulated the protein expressions of epithelial-mesenchymal transition (EMT) markers (N-cadherin and vimentin), and upregulated E-cadherin protein expression, which is involved in interrupting EGFR/Akt/ERK signaling pathways, as well as inhibiting COX-2 protein expression. All these results demonstrated that HDP might be a novel anti-metastatic agent for NSCLC treatment.

MicroRNA-183 induces epithelial-mesenchymal transition and promotes endometrial cancer cell migration and invasion in by targeting CPEB1.

The aim of this study is to evaluate the ability of microRNA-183 (miR-183) to influence epithelial-mesenchymal transition (EMT) and cell proliferation, migration, invasion, and apoptosis in endometrial cancer (EC) by targeting cytoplasmic polyadenylation element binding protein 1(CPEB1). EC tissues with matched nonmalignant tissues were collected from 208 EC patients. Ishikawa and RL95-2 cells were selected for cell experiments in vitro and each kind of cells were grouped into blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, CPEB1 overexpression, and miR-183 mimic + CPEB1 overexpression groups. Expressions of miR-183, CPEB1, E-cadherin, and Vimentin were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Cell viability, colony formation ability, migration, invasion, and apoptosis were assessed by MTT assay, clone formation assay, scratch test, Transwell assay, and flow cytometry. In vivo tumorigenesis of Ishikawa cells was evaluated by tumor formation in nude mice. The miR-183 expression was higher, but the CPEB1 expression was lower in EC tissues than in adjacent nonmalignant tissues. CPEB1 was confirmed as the target of miR-183 by dual-luciferase reporter assay. The miR-183 mimic group had increased cell viability, colony formation ability, cell invasion and migration, tumor volume and weight in nude mice, but decreased cell apoptosis when compared with the blank group. The expression of E-cadherin was down-regulate, but expression of Vimentin was up-regulate in the miR-183 mimic group in comparison with the blank group. In terms of a comparison between the blank group and CPEB1 overexpression group, the CPEB1 overexpression group had suppressed cell viability, colony formation ability, cell invasion and migration, tumor volume and weight, but increased cell apoptosis. The expression of E-cadherin was up-regulated, but the expression of Vimentin was down-regulated in the CPEB1 overexpression group in comparison with the blank group. The miR-183 mimic + CPEB1 overexpression group had higher miR-183 expression than the blank group. These findings indicate that miR-183 induces EMT, inhibits apoptosis, and promotes cell proliferation, migration, invasion, and in vivo tumorigenesis in EC by targeting CPEB1.

Transvaginal natural orifice transluminal endoscopic surgery tubal reanastomosis: a novel route for tubal surgery.

OBJECTIVE: To demonstrate how a transvaginal natural orifice transluminal endoscopic surgery (NOTES) tubal reanastomosis is a novel route for tubal surgery. The surgical technique is a combination of traditional vaginal surgery with single-site surgical skills. DESIGN: The surgical technique is explained in a stepwise fashion with the use of surgical video footage. The video uses a surgical case to demonstrate the specific techniques necessary to perform a NOTES tubal reanastomosis. SETTING: Teaching university. PATIENT(S): A 42-year-old female G2P2 with a history of tubal ligation 11 years before presentation requesting a tubal recanalization. INTERVENTION(S): Transvaginal NOTES tubal reanastomosis was initiated with a posterior colpotomy. A single-site gelport was placed. The fallopian tubes were hydrodissected, the blocked portion of each tube was removed, an epidural catheter was threaded through each lumen, and the two remaining segments of each tube were sutured together in an end-to-end fashion using single-site suturing skills. MAIN OUTCOME MEASURE(S): Transvaginal NOTES tubal reanastomosis as an alternative route for tubal reanastomosis. RESULT(S): The bilateral fallopian tubes were recanalized with bilateral tubal patency. This was confirmed 8 weeks postoperatively with a three-dimensional sonohystogram, which showed patency of the bilateral fallopian tubes. CONCLUSION(S): The current preferred technique for reversal of a tubal sterilization is to perform a minimally invasive surgery with an end-to-end anastomosis. This gives the patient a 60%-90% intrauterine pregnancy rate postoperatively. NOTES has the benefits of a fast recovery, no abdominal incisional pain, and an extremely cosmetic outcome. Current research has shown a 0%-3.1% range for the risk of pelvic infection in transvaginal NOTES if prophylactic antibiotics are administered during the surgery. The NOTES tubal reanastomosis combines the traditional vaginal surgery technique of creating a posterior colpotomy with single-site surgical skills like suturing and knot tying. The surgery is completed through a single transvaginal port without an abdominal incision. In the hands of a skilled minimally invasive surgeon, transvaginal NOTES tubal reanastomosis is a feasible and alternative route for this procedure.

Transvaginal Natural Orifice Transluminal Endoscopic Surgery Myomectomy: A Novel Route for Uterine Myoma Removal.

STUDY OBJECTIVE: Transvaginal surgery is the most minimally invasive surgery for a gynecologic procedure, but it has the limitation of lack of exposure and limited surgical space when using traditional vaginal surgical instrumentation, such as in a hysterectomy for a uterus without descent or for a myomectomy. Transvaginal natural orifice transluminal endoscopic surgery (NOTES) offers similar benefits of traditional vaginal surgery but also expands the horizon of transvaginal surgery by allowing the surgeon to perform procedures that are typically limited to an abdominal approach. The advantages of NOTES may include no incisional pain as well as a better cosmetic outcome. These benefits help outweigh the obstacle of learning this novel approach. Our objective is to demonstrate the transvaginal NOTES technique as a combination of traditional vaginal surgical skill with single-site surgical skill. DESIGN: Stepwise demonstration of the transvaginal NOTES technique for myomectomy with narrated video footage (Canadian Task Force classification III). SETTING: Academic tertiary care hospital. PATIENT: A 42-year-old woman. INTERVENTIONS: Transvaginal NOTES myomectomy with combined transvaginal surgical and single-site surgical skills. MEASUREMENTS AND MAIN RESULTS: A 42-year-old woman (gravida 2 para 2) with a preoperative transvaginal ultrasound diagnosis of a 6-cm left anterior myoma requested myoma removal with uterine preservation. She presented with a 2-year history of left pelvic pain and menorrhagia. The myoma was removed with minimal blood loss, and pathology revealed a necrotic myoma. The patient had resolution of her left-sided pelvic pain. CONCLUSIONS: Combined with traditional transvaginal anterior colpotomy, single-site surgical skills allow the surgeon to access the entire abdomen and perform myomectomy through a transvaginal single port. Transvaginal NOTES myomectomy is not only possible but allows myomectomy to be performed with no abdominal incision.

Effects of exogenous IL-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T cells.

BACKGROUND: This study aims to investigate the effects of exogenous interleukin (IL)-37 on the biological characteristics of human lung adenocarcinoma A549 cells and the chemotaxis of regulatory T (Treg) cells. METHODS: After isolating the CD4+ CD25+ Treg cells from the peripheral blood, flow cytometry was used to detect the purity of the Treg cells. A549 cells were divided into blank (no transfection), empty plasmid (transfection with pIRES2-EGFP empty plasmid) or IL-37 group (transfection with pIRES2-EGFP-IL-37 plasmid). RT-PCR was used to detect mRNA expression of IL-37 and ELISA to determine IL-37 and MMP-9 expressions. Western blotting was applied to detect the protein expressions of PCNA, Ki-67, Cyclin D1, CDK4, cleaved caspase-3 and cleaved caspase-9. MTT assay, flow cytometry, scratch test and transwell assay were performed to detect cell proliferation, cycle, apoptosis, migration and invasion. Effect of exogenous IL-37 on the chemotaxis of Treg cells was measured through transwell assay. Xenograft models in nude mice were eastablished to detect the impact of IL-37 on A549 cells. RESULTS: The IL-37 group had a higher IL-37 expression, cell apoptosis in the early stage and percentage of cells in the G0/G1 phase than the blank and empty plasmid groups. The IL-37 group had a lower MMP-9 expression, optical density (OD), percentage of cells in the S and G2/M phases, migration, invasion and chemotaxis of CD4+CD25+ Foxp3+ Treg cells. The xenograft volume and weight of nude mice in the IL-37 group were lower than those in the blank and empty plasmid groups. Compared with the blank and empty plasmid groups, the IL-37 group had significantly reduced expression of PCNA, Ki-67, Cyclin D1 and CDK4 but elevated expression of cleaved caspase-3 and cleaved caspase-9. CONCLUSION: Therefore, exogenous IL-37 inhibits the proliferation, migration and invasion of human lung adenocarcinoma A549 cells as well as the chemotaxis of Treg cells while promoting the apoptosis of A549 cells.

Cisplatin regulates cell autophagy in endometrial cancer cells via the PI3K/AKT/mTOR signalling pathway.

Endometrial cancer is the most common gynaecological malignancy encountered in developed countries and the second most common in the developing world. The five-year survival rate of patients with endometrial cancer diagnosed at a late stage is <30%. Therefore, it is critical to develop a suitable chemotherapeutic regimen for late-stage endometrial cancer. Cisplatin (CDDP) is a first-line chemotherapeutic drug for endometrial cancer chemotherapy. The present study investigated the molecular mechanism underlying the effect of CDDP on endometrial cancer from the perspective of cell autophagy. Ishikawa cells were treated with 10, 20, 40 or 80 µg/ml CDDP for 12, 24, 48 and 72 h. The cells were then harvested and subjected to cell proliferation assays. Based on the results, 20 µg/ml CDDP was selected as the treatment used for 12 and 24 h for the assays. To detect the effect of CDDP on Ishikawa cell autophagy, autophagosome formation was observed using a transmission electron microscope, and the expression level of autophagy-related gene microtubule-associated protein 1 light chain 3α, was examined using immunofluorescence microscopy. The results demonstrated that CDDP treatment promoted cell autophagy in Ishikawa cells. In addition, the total and phosphorylated protein levels of phosphoinositide 3-kinase (PI3K) p85, protein kinase B (AKT) and mammalian target of rapamycin (mTOR), the key proteins of the PI3K/AKT/mTOR signalling pathway, were detected by western blot analysis. The results indicated that CDDP treatment inactivated the PI3K/AKT/mTOR signalling pathway. To further examine whether CDDP affects cell autophagy in Ishikawa cells via the PI3K/AKT/mTOR signalling pathway, the cells were co-treated with a PI3K activator, insulin-like growth factor-1 (IGF-1). The results demonstrated that IGF-1 co-treatment reversed the effect of CDDP on cell autophagy in Ishikawa cells. In brief, the present study hypothesized that CDDP may regulate cell autophagy in the Ishikawa endometrial cancer cell line via the PI3K/AKT/mTOR signalling pathway.

A Multi-Step miRNA-mRNA Regulatory Network Construction Approach Identifies Gene Signatures Associated with Endometrioid Endometrial Carcinoma.

We aimed to identify endometrioid endometrial carcinoma (EEC)-related gene signatures using a multi-step miRNA-mRNA regulatory network construction approach. Pathway analysis showed that 61 genes were enriched on many carcinoma-related pathways. Among the 14 highest scoring gene signatures, six genes had been previously shown to be endometrial carcinoma. By qRT-PCR and next generation sequencing, we found that a gene signature (CPEB1) was significantly down-regulated in EEC tissues, which may be caused by hsa-miR-183-5p up-regulation. In addition, our literature surveys suggested that CPEB1 may play an important role in EEC pathogenesis by regulating the EMT/p53 pathway. The miRNA-mRNA network is worthy of further investigation with respect to the regulatory mechanisms of miRNAs in EEC. CPEB1 appeared to be a tumor suppressor in EEC. Our results provided valuable guidance for the functional study at the cellular level, as well as the EEC mouse models.

Influence of gonadotropin-releasing hormone agonist on the effect of chemotherapy upon ovarian cancer and the prevention of chemotherapy-induced ovarian damage: an experimental study with nu/nu athymic mice.

BACKGROUND AND OBJECTIVE: Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. METHODS: nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). RESULTS: Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). CONCLUSIONS: Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.