Participation of Long Noncoding RNA FOXP4-AS1 in the Development and Progression of Endometrioid Carcinoma with Epigenetically Silencing DUSP5.

Background: Long noncoding RNAs (lncRNAs), as emerging regulators of a wide variety of biological processes via diverse mechanisms, have been demonstrated to be of increasing importance in biology. Genome-wide association studies of tumor samples have identified several lncRNAs as either oncogenes or tumor suppressors in various types of cancers. In recent years, the importance of lncRNAs, especially in endometrioid cancer (EEC), has become increasingly well understood. The lncRNA Forkhead box P4 antisense RNA 1 (FOXP4-AS1) has been reported to fulfill roles in several types of cancers; however, the main biological function and associated underlying molecular mechanism of FOXP4-AS1 in EEC have yet to be fully elucidated. Materials and Methods: The present study therefore aimed to investigate how RNA FOXP4-AS1 may participate in the development and progression of endometrioid carcinoma tissues. To meet this aim, in the present study, the expression level of FOXP4-AS1 was investigated in endometrioid carcinoma tissues and matching nearby normal endometrial tissues collected from patients receiving surgery at the hospital, and a series of molecular biological assays were performed to investigate the effect of FOXP4-AS1 on cell proliferation, cell migration, and cell invasion, and so on. Results: An increased concentration of FOXP4-AS1 was identified in endometrioid carcinoma samples and cell lines compared with the corresponding controls, and this lncRNA was found to be positively correlated with advanced FIGO stages in patients with endometrial cancer. Furthermore, knocking down endogenous FOXP4-AS1 led to a significant reduction in the colony formation number and a significant inhibition of cell proliferation, cell migration, and cell invasion in endometrioid carcinoma cells. Moreover, dual-specificity phosphatase 5 (DUSP5), which is lowly expressed in endometrioid carcinoma tissues cells and negatively modulated by FOXP4-AS1, was identified as the downstream target molecule of FOXP4-AS1. Subsequently, the mechanistic experiments confirmed that, through binding to enhancer of zeste homolog 2 (EZH2; one of the catalytic subunits of polycomb repressive complex 2 [PRC2]), FOXP4-AS1 could epigenetically suppress the expression of DUSP5. Finally, the oncogenic function of the FOXP4-AS1/EZH2/DUSP5 axis in endometrioid carcinoma was confirmed via rescue assays. Conclusions: The findings of the present study have highlighted how FOXP4-AS1 fulfills an oncogenic role in endometrioid carcinoma, and targeting FOXP4-AS1 and its pathway may provide new biomarkers for patients with endometrioid carcinoma.

Comparing the survival rates of patients with stage IIIC endometrial cancer undergoing sandwich therapy to those undergoing sequential chemotherapy and radiotherapy: a meta-analysis.

BACKGROUND: The use of additional treatment after surgery for stage IIIC endometrial cancer (EC) according to the Federation of Gynecology and Obstetrics (FIGO) is still a topic of discussion. This meta-analysis examined the effects of sandwich treatment and sequential treatment on the survival of individuals diagnosed with stage IIIC EC. METHODS: We examined the literature from various databases regarding the overall survival (OS) and adverse effects of the two additional therapies following surgery in individuals diagnosed with stage IIIC EC. Revman 5.4.1 was utilized to combine hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI) for OS and toxicities. RESULTS: The findings comprised of five retrospective investigations involving a combined total of 800 individuals. The patients who underwent sandwich treatment did not demonstrate a notable improvement in survival rates over a period of 3 years. Upon eliminating the impact of extensive samples, it was discovered that sandwich therapy exhibited a superior 5-year overall survival compared to patients receiving sequential therapy. The effectiveness of sandwich therapy was superior to sequential therapy in terms of a 3-year OS for non-endometrioid histology, although the outcome did not reach statistical significance. The toxicities of both treatments were similar. CONCLUSIONS: In terms of long-term survival, sandwich therapy was found to be more advantageous than sequential therapy for patients with stage IIIC EC, with no significant disparity observed in the 3-year OS and toxicities between the two treatments. Sandwich therapy exhibited a tendency towards improved effectiveness in patients with histology other than endometrioid.

Protein anabolism is key to long-term survival in high-grade serous ovarian cancer.

This study aimed to identify the biological processes associated with long-term survival in high-grade serous ovarian cancer (HGSOC). HGSOC cases obtained from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) database were divided into long-term survivors (LTS) and normal-term survivors (NTS) based on survival cutoffs defined by the HGSOC cohort in the SEER database. Differentially expressed genes (DEGs) were screened using the generalized linear modeling (GLM) method. Gene Ontology (GO) functional and KEGG pathway enrichment analyses were performed using DAVID Bioinformatics Resources. DEG-related protein-protein interactions (PPI) were extracted from the STRING database and hub genes were identified using CytoHubba in the Cytoscape program. In total, 157 DEGs, including 155 upregulated and 2 downregulated genes, were identified. Upregulated genes were statistically enriched in 80 GO terms and 11 KEGG pathways related to energy and substrate metabolism, such as protein absorption, digestion, and metabolism as well as signaling pathways, including chromatin silencing, regulation of ERK1 and ERK2 cascade, and regulation of MAPKKK. ALB and POMC were the common hub genes. These findings reveal that protein anabolism is crucial to long-term survival, regulated by activation of the MAPK/ERK signaling pathway and chromatin silencing. Comprehensive understanding of the molecular mechanisms via further exploration may contribute toward an effective treatment for ovarian cancer.

Prevalence and occult rates of uterine leiomyosarcoma.

This study aimed to assess the prevalence and occult rates of uterine leiomyosarcoma (ULMS) in women with smooth-muscle tumors undergoing gynecological surgery. A retrospective study was performed at an academic cancer center from 2008 to 2015. Patients undergoing either hysterectomy or myomectomy via laparoscopic, abdominal, vaginal, and hysteroscopic approaches were identified with the validated pathology diagnosis of either ULMS or leiomyomas. All patients initially operated at our institute were included and reviewed. The prevalence and occult rates of ULMS were calculated and compared between different age groups.Twenty-eight patients with original ULMS were identified in 9556 gynecological surgeries. The prevalence of overall and occult ULMS in our study was 0.25% (1 in 345 patients) and 0.07% (1 in 1429 patients). The proportion of occult in all ULMSs was 25%. The prevalence rates of overall ULMS were 0.21%, 0.13%, 0.52%, 2.12%, and 6.67% in the 30 to 39, 40 to 49, 50 to 59, 60 to 69, and ≥70-year age groups, respectively. There was a significantly increased risk of ULMS after 50 years of age. The prevalence rates of occult ULMS were 0.05%, 0.08%, and 0.12% for the 30 to 39, 40 to 49, and 50 to 59 year age groups, respectively. There was no statistically significant difference among age the groups. The prevalence of ULMS was 0.41% and 0.16% for solitary and multiple tumor masses, respectively. Patients with solitary uterine tumors were at a significantly increased risk of ULMS (OR = 2.601, 95% CI = 1.108-6.141).Our retrospective data in part reflects the clinical characteristics of overall and occult ULMS and forms the basis for further prevention of occult ULMS.

CARLo-5 as an oncogenic gene in endometrial carcinoma.

The long noncoding RNA CARLo-5 is dysregulated in multiple types of human cancers. High CARLo-5 is a promising predictive factor for various cancers, including endometrial carcinoma (EC). Our previous study showed that the expression level of CARLo-5 was associated with advanced FIGO stage (The International Federation of Gynecology and Obstetrics), lymph node metastasis, and the poor survival of patients with EC. In the present study, we demonstrated that the downregulation of CARLo-5 could affect the proliferation, cell cycle, migration, and invasion of EC cell lines HEC-1B and KLE cells. The oncogenic activity of CARLo-5 was also confirmed with in vivo data. Mechanistically, CARLo-5 could affect the expression of CDK/CDKN1A and MMP2/9, which have been reported to be regulated by CARLo-5 and associated with cell cycle and motility. In conclusion, this study is the first to discover the biological function and mechanism of CARLo-5 in regulating the biological characteristics of EC cells. Targeting CARLo-5 and its pathway might provide new biomarkers or potential therapies target for patients with EC. Environ. Mol. Mutagen. 61:256-265, 2020. © 2019 Wiley Periodicals, Inc.

Analysis of the relationship between COMT polymorphisms and endometriosis susceptibility.

This study was aimed to explore the correlation between catechol-O-methyltransferase (COMT) gene polymorphisms and endometriosis susceptibility in Chinese Han population.This case-control study recruited 134 endometriosis patients and 139 healthy individuals. COMT gene rs4680, rs2020917, and rs4646312 polymorphisms in the subjects were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Association between COMT polymorphisms and endometriosis susceptibility was evaluated by χ test and adjusted by Logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to present the relative risk of endometriosis.A allele of rs4680 was distinctly correlated with increased susceptibility of endometriosis (OR = 1.450, 95% CI = 1.012-2.076). However, when adjusted by the confounding factors, these associations become not significant. We failed to find any significant association between rs2020917 and endometriosis risk in the crude results. The adjusted results suggested that rs2020917 TT genotype and T allele were distinctly correlated with enhanced endometriosis risk (TT vs CC: P = .038, OR = 2.894, 95% CI = 1.060-7.903; T vs C: P = .039, OR = 1.481, 95% CI = 1.021-2.149). Besides, rs4646312 C allele was significantly correlated with endometriosis risk both in the crude (P = .027, OR = 1.502, 95% CI = 1.047-2.154) and adjusted (P = .019, OR = 1.564, 95% CI = 1.078-2.269) results.COMT polymorphisms might predict the occurrence of endometriosis.