GLP1R boosts survival, migration and invasion of endometrial cancer cells and protects against ferroptotic cell death.

BACKGROUND: Despite the strong evidence concerning carcinogenic roles of glucagon-like peptide 1 receptor (GLP1R), the role of this gene in endometrial cancer (EC) remains elusive. This study investigated the properties of GLP1R on EC in vitro. METHODS: The expression of GLP1R in EC was detected by RT-qPCR, immunohistochemistry, and western blotting. Cell viability, cell cycle, apoptosis, migration, invasion and ferroptosis were assessed through CCK-8, flow cytometry, wound healing, transwell, DCFH-DA and western blotting, respectively. RESULTS: We found that GLP1R was up-regulated in EC than normal specimens. It had the highest expression in AN3CA cells. Cell viability, migration and invasion were significantly reduced, while cell cycle arrest and apoptosis were induced following GLP1R knockdown. The malignant biological behaviours of AN3CA cells were investigated when treated with exendin-4 (GLP1R agonist). Moreover, GLP1R lowered intracellular ROS level and expression of SLC7A11, and FTH1, but mitigated GPX4 expression in AN3CA cells. CONCLUSION: In a word, GLP1R was up-regulated in EC and its up-regulation facilitated the proliferative and metastatic potentials, and protected cells from ferroptosis, thereby accelerating EC progression. These data emphasised the potency of GLP1R as a therapeutic agent against EC.

Endometrial cancer (EC) is the second most common form of gynaecologic malignancy, with over 189,000 new cases and about 45,000 deaths worldwide per annum. The effects of glucagon-like peptide 1 receptor (GLP1R) in cancers such as colon and pancreatic cancers have been uncovered. However, whether GLP1R affects EC progression especially ferroptosis process remains elusive. In this study, up-regulation of GLP1R promotes the proliferative and metastatic potentials of EC cells, and protects EC cells from ferroptosis. The opposite results are observed in GLP1R knocking-down. Our study found that GLP1R may exert an oncogene function in EC cells, which can affect proliferative, migrated as well as invasive capacities of EC cells. Moreover, it protected EC cells from ferroptosis. Thus, our results expanded the understanding of the function of GLP1R protein and offered insights into the targeted treatment strategies against EC.

Bazedoxifene plus conjugated estrogens improve menopausal symptoms in postmenopausal women: a systematic review and meta-analysis.

Our aim is to evaluate the efficacy of bazedoxifene (BZA) plus conjugated estrogens (CE) on menopausal symptoms in postmenopausal women. A series of databases including PubMed, EMBASE, Medline, Web of science, China national knowledge internet and Wanfang database up to 31 October 2021 were searched, and randomized controlled trials (RCTs) of BZA/CE for menopausal symptoms were included. Seven RCTs involving 5431 patients were included in this study. Compared with placebo group, there were significantly reduce in daily number of hot flushes, daily number of moderate or severe hot flushes, the percentages of parabasal cells and the time to fall sleep when patients treated with BZA/CE. Besides, there were significant improvement in sleep disturbance and total MENQOL. However, no significant improvements in sleep adequacy were observed in the three groups. Furthermore, BZA 20 mg/CE 0.625 mg was more effective than BZA 20 mg/CE 0.45 mg in improving the menopausal symptoms. Therefore, both bazedoxifene 20 mg plus conjugated estrogens 0.45 mg and bazedoxifene 20 mg plus conjugated estrogens 0.625 mg could significantly improve the menopause-related symptoms and MENQOL in postmenopausal women, and the curative effects of BZA 20 mg/CE 0.625 mg were better than that of BZA 20 mg/CE 0.45 mg. These findings need to be further confirmed by more high-quality RCTs.

GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP/PKA pathway.

BACKGROUND: This study strived to explore the role and mechanism of glucagon-like peptide-1 receptor (GLP1R) in endometrial carcinoma (EC). METHODS: In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95-2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p-PKA, and PKA) were determined by enzyme-linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC. RESULT: According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway. CONCLUSION: Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.

Analysis on clinical association of uterine scar diverticulum with subsequent infertility in patients underwent cesarean section.

ABSTRACT: To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ±â€Š0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ±â€Š0.90 vs 0.47 ±â€Š0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ±â€Š1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1ß, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors.

LncRNA CASC15 Functions As An Unfavorable Predictor Of Ovarian Cancer Prognosis And Inhibits Tumor Progression Through Regulation Of miR-221/ARID1A Axis.

BACKGROUND: LncRNA cancer susceptibility candidate 15 (CASC15) has been demonstrated to act as an oncogene in different cancers; however, its role in ovarian cancer remains elusive. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA CASC15. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of lncRNA CASC15. CCK-8, soft-agar colony-formation, flow cytometry, transwell migration and invasion assays were used to analyze the biological behavior of lncRNA CASC5 in ovarian cancer. Furthermore, the potential mechanism of lncRNA CAC15 was investigated by bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay. RESULTS: In this study, we found that the expression of CASC15 was lower in ovarian cancer tissues and cells by qRT-PCR. In addition, low expression of CASC15 was closely correlated with advanced TNM stage, moderate/poor differentiation, and larger size. Moreover, Kaplan-Meier survival analysis showed that patients with low CASC15 expression level had poorer overall survival and progression-free survival than those with high CASC15 expression. Meanwhile, ROC analysis found that CASC15 had diagnostic values to distinguish tumor tissues from nontumorous tissues. Overexpression of CASC15 prohibited the malignancy of ovarian cancer cells, including proliferation, colony formation, cell cycle, migration, and invasion, and promoted cell apoptosis. In addition, bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay confirmed that CASC15 straightly interacted with miR-221. We also observed that ARID1A was a downstream target of miR-221 and CASC15 subsequently exerted its tumor-suppressive effects by regulating the expression of ARID1A in ovarian cancer cells. CONCLUSION: Overall, this study firstly elucidated that CASC15 could play a tumor-suppressive role in ovarian cancer by the regulation of CASC15/miR-221/ARID1A axis, which may provide a ponderable prognostic biomarker and promising therapeutic target for treatment of patients with ovarian cancer.