KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1.

Endometriosis is increasingly affecting women worldwide and research is focusing on identifying key targets in its pathogenesis. Changes in succinylation genes regulate the function of this protein and further influence the development of the disease. However, the role of succinylation genes in endometriosis is not clear from current studies. The expression of succinylation genes was determined in ectopic endometrium (EC) and ectopic patients with uterine fibroids (EN) by real-time quantitative PCR (qRT-PCR) and Western blot. Cell Counting Kit-8, transwell assays, and flow cytometry were used to assess endometrial stromal cells (ESCs) proliferation, apoptosis, migration, and invasion. KAT2A and ENO1 association was detected by qRT-PCR, immunofluorescence, and CoIP. We found that gene and protein levels of KAT2A were significantly increased in the EC group compared to EN group tissues. KAT2A silencing inhibited cell proliferation, migration, and invasion and promoted apoptosis. Western blot results showed that the expression of ENO1 and its succinylation was significantly upregulated in ECSc after KAT2A overexpression. CoIP results showed that KAT2A is positively bound to ENO1. Immunofluorescence also showed co-localized expression of KAT2A with ENO1. Furthermore, ENO1 overexpression reversed the effects of KAT2A silencing on the malignant behavior of ESCs. In summary, we found that succinylation of ENO1 mediated by KAT2A played a role in promoting the progression of endometriosis.

Comprehensive Analysis Identifies the PPAR-Targeted Genes Associated with Ovarian Cancer Prognosis and Tumor Microenvironment.

Background: There is a significant role for peroxisome proliferator-activated receptors (PPARs) in the development of cancer. Nevertheless, the role of PPARs-related genes in ovarian cancer (OC) remains unclear. Methods: The open-accessed data used for analysis were downloaded from The Cancer Genome Atlas database, which was analyzed using the R software. Results: In our study, we comprehensively investigated the PPAR target genes in OC, including their biological role. Meanwhile, a prognosis signature consisting of eight PPAR target genes was established, including apolipoprotein A-V, UDP glucuronosyltransferase 2 family, polypeptide B4, TSC22 domain family, member 1, growth hormone inducible transmembrane protein, renin, dedicator of cytokinesis 4, enoyl CoA hydratase 1, peroxisomal (ECH1), and angiopoietin-like 4, which showed a good prediction efficiency. A nomogram was constructed by combining the clinical feature and risk score. Immune infiltration and biological enrichment analysis were applied to investigate the difference between high- and low-risk patients. Immunotherapy analysis indicated that low-risk patients might respond better to immunotherapy. Drug sensitivity analysis indicated that high-risk patients might respond better to bleomycin, nilotinib, pazopanib, pyrimethamine, and vinorelbine, yet worse to cisplatin and gefitinib. Furthermore, the gene ECH1 was selected for further analysis. Conclusions: Our study identified a prognosis signature that could effectively indicates patients survival. Meanwhile, our study can provide the direction for future studies focused on the PPARs in OC.

Dysregulated microRNAs involved in the progression of cervical neoplasm.

PURPOSE: MicroRNAs (miRNAs) exhibit dysregulated expression in human cancer and play an important role in carcinogenesis. The aim of this study was to identify a distinct miRNA expression signature for cervical cancer and cervical intraepithelial neoplasia (CIN) and to investigate the function of deregulated miRNAs in cervical carcinoma. METHODS: A miRNA microarray was used to compare miRNA expression profiles in cervical cancer, CIN and normal cervical tissues. Real-time RT-PCR was used to validate the expression of 9 miRNAs in 103 cervical tissues. Bioinformatics programs were used to predict potential target genes and their function. Functional studies were performed to characterize the effect on cervical cancer cells by overexpression of miR-218 and miR-21. RESULTS: We identified deregulated miRNAs in cervical cancer and high-grade squamous intraepithelial lesions (HSIL). MiR-218 was the most downregulated (0.175-fold decrease) miRNA, and miR-21 was the most upregulated (5.67-fold increase) miRNA. In addition, the expression patterns of 9 miRNAs were validated by real-time RT-PCR. Bioinformatics analyses and functional studies indicated that miR-218 and miR-21 may be involved in cancer invasion and metastasis. CONCLUSION: Our study demonstrated that miRNAs are aberrantly expressed in cervical cancer and cervical preneoplastic lesions. These miRNAs may be involved in the progression of cervical neoplasm as potential tumor suppressor genes or oncogenes.

[Efficacy and safety of GnRH-a combine with laparoscope conservative surgery in the treatment of the moderate or severe endometriosis].

OBJECTIVE: To study the efficacy and safety of Gonadotropin-releasing hormone agonists (GnRH-a) combined with laparoscope conservative surgery in treatment of moderate or severe endometriosis. METHODS: From Jan. 2007 to Jan. 2010, 68 patients with moderate or severe undergoing treatment in Renmin Hospital of Wuhan University were enrolled in this retrospective study. Three groups were classified, which were 25 patients in GnRH-a group, subcutaneous injection Leuprorelin on the second day of menstruation, every 4 weeks for 3 months. Twenty-three patients in Marvelon group, orally one marvelon tablet on the second day of menstruation, continuous 21 days for one period of treatment for 3 courses. Twenty patients in surgery group, without any medicine used preoperatively. All patients were followed by 12 months and compare their surgery time, blood loss, recovery, visual analog scale (VAS), and recurrence and so on. RESULTS: The operating time were (68 ± 18) min in GnRH-a group, (80 ± 21) min in Marvelon group and (90 ± 24) min in surgery group. The amount of bleeding were (118 ± 15) ml in GnRh-a group, (161 ± 18) ml in Marvelon group and (193 ± 13) ml in surgery group. There was significant lower in the operating time and amount of bleeding in GnRH-a group than those in other two groups (P < 0.05). The activity time and the anus exhaust time were shorter in patients in GnRh-a group than those in the other two groups significantly (P < 0.05). When followed up in 12 months after treatment, visual analogue scale had dropped from 3.8 (1.9 - 6.8) to 1.9 (1.1 - 2.8) in GnRh-a group, from 2.7 (1.3 - 5.5) to 1.8 (1.2 - 3.2) in Marvelon group and from 1.9 (1.0 - 4.9) to 1.6 (1.0 - 3.6) in surgery group. It was showed the most remarkable decreased VAS in GnRHa group when compared with the other two groups (P < 0.05). The recurrence rates were 12% (3/25) in GnRH-a group, 22% (5/23)in Marvelon group and 25% (5/25) in surgery group. It was found that the most significant lower recurrence was in GnRH-a group when compared with the other two groups (P < 0.05). CONCLUSIONS: It was safe and efficacy that GnRH-a combined with laparoscopic conservative surgery were used in treatment of endometriosis. It could bring shorter operation time, less intraoperative blood loss, quick postoperative recover, the lower recurrence rate.