BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy. and the prognosis of advanced EC is unsatisfactory. The deregulated expression of RNA-binding proteins (RBPs) is closely associated with the occurrence and development of cancer. However, the role of RBPs in EC remains unclear. The aim of this study was to validate the prognostic values of RBPs combined with clinical factors.METHODS: We downloaded the RNA sequencing and clinical data for EC from The Cancer Genome Atlas (TCGA) database. R software was used to identify the differentially expressed RBPs. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the 4 overall survival (OS)-related RBPs. We then constructed a nomogram combining the 4-RBP signature with clinical risk factors to assess the prognostic power. Furthermore, we validated the expression of 4 RBPs in our patient samples using quantitative real-time polymerase chain reaction (qRT-PCR) and explored the effect of cold-inducible RNA-binding protein (CIRBP) on EC tumor growth using cell proliferation experiments.RESULTS: It is found that Shwachman-Bodian-Diamond syndrome (SBDS), CIRBP, MRPL15, and CELF4 were significantly related to the prognosis of EC patients. In addition. the nomogram showed better performance in OS predictions than the International Federation of Gynecology and Obstetrics (FIGO) stage. The qRT-PCR results showed that low CIRBP expression was associated with cell proliferation.CONCLUSIONS: In our study. we constructed a 4-RBP signature-based nomogram combined with clinical factors in EC that could effectively predict the prognosis of EC patients. The results provide novel insights into the development of treatment targets and prognostic molecular markers in EC.

Cervical cancer is the most common gynecological cancer in women worldwide. Human papillomavirus (HPV) is required but not sufficient for developing cervical cancer. HPV E6 and E7 proteins are able to directly interact with certain nuclear receptors; however, whether steroid hormone receptors mediate cervical carcinogenesis is not completely understood. The present study demonstrated via immunohistochemistry that estrogen receptor alpha (ER alpha) and androgen receptor (AR) expression were decreased in a sequential manner from healthy cervical tissues to cervical intraepithelial neoplasia tissues and further to cervical cancer (CC) tissues, whereas microRNA (miR)-130a-3p expression levels were higher in CC tissues compared with healthy tissues. Both ER alpha and AR were direct targets of miR-130a-3p, as determined by performing luciferase reporter assays and western blotting. Functionally, compared with the corresponding control groups, miR-130a-3p knockdown, ER alpha overexpression and AR overexpression significantly inhibited CC cell proliferation and invasion, as demonstrated by the results obtained from the Cell Counting Kit-8 and Transwell assays in vitro. In addition, antagomiR-130a decreased tumor size and weight in vivo compared with control antagomiR as determined via the xenograft tumor growth assay. Therefore, the results suggested that miR-130a-3p might contribute to tumor progression by suppressing ER alpha and AR, and serve as a promising candidate target for the treatment of patients with CC.

目的基于内源性竞争性网络分析可用于子宫内膜癌(EC)分型及诊治的潜在生物标志物。方法从TCGA数据库中总结EC差异表达的基因,筛选出32个基因来构建内源性竞争性网络。采用基因本体论(GO)和京都基因与基因组数据库(KEGG)富集分析、相关

AMPH1, an abundant protein in nerve terminals, plays a critical role in the recruitment of dynamin to sites of clathrin-mediated endocytosis. Recently, it is reported to be involved in breast cancer and lung cancer. However, the impact of AMPH1 on ovarian cancer is unclear. In this study, we used gain-of-function and loss-of-function methods to explore the role of AMPH1 in ovarian cancer cells. AMPH1 inhibited ovarian cancer cell growth and cell migration, and promoted caspase-3 activity, resulting in the increase of cell apoptosis. In xenograft mice model, AMPH1 prevented tumour progression. The anti-oncogene effects of AMPH1 on ovarian cancer might be partially due to the inhibition of PI3K/AKT signalling pathway after overexpression of AMPH1. Immunohistochemistry analysis showed that the staining of AMPH1 was remarkably reduced in ovarian cancer tissues compared with normal ovarian tissues. In conclusion, our study identifies AMPH1 as a tumour suppressor in ovarian cancer in vitro and in vivo. This is the first evidence that AMPH1 inhibited cell growth and migration, and induced apoptosis via the inactivation of PI3K/AKT signalling pathway on ovarian cancer, which may be used as an effective strategy.

Background: Perineural invasion (PNI) is correlated with negative prognosis in multiple cancers, but its role in endometrial cancer (EC) is still largely unknown; thus, targeted treatment for nerve infiltration is lacking as well.Methods: The interaction between nerve and EC cells were investigated by in vitro neural invasion assay and transwell coculture system. Then the nerve-related receptor gene glutamate ionotropic receptor AMPA type subunit 2 (GRIA2) was detected in EC tissues and cells using PCR array, western blotting, and immunohistochemistry. The role of GluR2 (gene name GRIA2) on EC proliferation, migration and invasion was evaluated by a GluR2 antagonist and shRNA. At the same time, the neurotransmitter effect on GluR2 (glutamate) from the cocultured conditional medium was measured using high-performance liquid chromatography (HPLC).Results: EC cell line Ishikawa (ISK) showed the ability to migrate along neurites in vitro and the numbers of migrated/invaded EC cells in the DRG neuron coculture group were significantly increased. The expression of GluR2 in EC tissue was found to be higher than that in para-carcinoma tissue. After GluR2 antagonist and GluR2 shRNA treatment, the proliferation, migration and invasion of ISK cells was markedly inhibited. Moreover, the ability of DRG neurons to promote the migration and invasion of ISK cells could also be attenuated by downregulation of GIuR2, and the concentration of the neurotransmitter glutamate was notably increased in the coculture conditional medium compared to that in the DRG neuron or ISK cells alone.Conclusions: DRG neurons promote metastasis of EC cells via GluR2, which might be a risk factor for PNI in EC. Moreover, the perineural system may promote tumor invasion and metastasis under certain circumstances.

Ovarian cancer is one of the deadliest gynecological cancer, with a low overall 5-year survival rate. RDM1, RAD52 motif-containing protein 1, is sensitive to cisplatin, a common chemotherapy drug and it has an important role inDNA damage repair pathway. Until now, the effect of RDM1 in ovarian cancer is undiscovered. Here, clinical data shows that the tumour tissues of ovarian carcinoma patients with higher mRNA and protein expression of RDM1. Knockdown of RDM1 in ovarian carcinoma cells reduces cell proliferation and promotes apoptosis, consistent with the role RDM1 in the overexpression experiments. The research of xenograft mouse model shows stable knockdown of RDM1 significantly inhibits ovarian cancer tumour growth. These in vitro and in vivo results conclude that RDM1 plays an oncogenic role in human ovarian carcinoma. Interestingly, p53/RAD51/RAD52 signalling pathway can be regulated by RDM1, and the negative regulation of p53 by RDM1 may be one of major mechanisms for RDM1 to accomplish its oncogenic functions in ovarian carcinoma. Therefore, RDM1 may be a new target for the treatment of ovarian carcinoma.
© 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Endometrial cancer is one of the most common gynecological malignant tumors. The roles of competing endogenous RNAs (ceRNAs) in this disease, however, remain unclear. In this study, we constructed a ceRNA network to reveal the core ceRNAs in endometrial cancer. Differentially expressed genes were summarized from The Cancer Genome Atlas database, whereupon 140 genes were identified for building the network. Further correlation, survival, and enrichment analyses suggested that these genes may help towards elucidating the molecular mechanisms of endometrial cancer. After validation of the findings with the GSE17025 data set, LINC00958, microRNA-761, and DOLPP1 were highlighted as the critical genes in the ceRNA network. Our work suggests that LINC00958 may regulate DOLPP1 by "sponging" miR-761 in endometrial cancer.

Background Progestin is effective to promote endometrial cancer (EC) cells apoptosis, however, continuous progestin administration causes low level of progestin receptor B (PRB), further resulting in progestin resistance. Here, we performed microarray analysis on Ishikawa cells (PRB+) treated with medroxyprogesterone acetate (MPA) to explore the molecular mechanism underlying the inhibitory influence of MPA on PRB+ EC cells. Methods Microarray analysis was performed by using Ishikawa cells (PRB+) treated with MPA. Differentially expressed mRNA and long noncoding RNAs (lncRNAs) were identified. Furthermore, the functions of these mRNAs and lncRNAs were predicted by functional enrichment analysis. QRT-PCR was further performed to verify the microarray data. Results A total of 358 differentially expressed genes and 292 lncRNAs were identified in Ishikawa cells (PRB+) treated with MPA. QRT-PCR verified these data. Functional enrichment analysis identified endoplasmic reticulum (ER) stress as the key pathway involved in the inhibitory effect of MPA on EC cells. And the ER stress apoptotic molecule CHOP and ER stress related molecule HERPUD1 were both highly expressed in Ishikawa cells (PRB+) treated with MPA. Co-expression analysis showed lnc-CETP-3 was highly correlated with CHOP and HERPUD1, suggesting it might participate in ER stress pathway-related EC cell apoptosis caused by MPA. In addition, compared with untreated cells, lnc-CETP-3, CHOP and HERPUD1 were significantly up-regulated in Ishikawa cells (PRB+) treated with MPA, whereas they have no statistical significance in KLE cells (PRB-). Conclusions MPA may activate ER stress by progesterone-PRB pathway to up-regulate CHOP expression, which may be one of the molecular mechanisms underlying the inhibitory effect of MPA on EC cells with PRB+. Lnc-CETP-3 might be involved in this process. These findings may provide therapeutic targets for EC patients with PRB-, and resistance-related targets to increase the sensitivity of MPA on EC cells.

目的探讨1型胰岛素样生长因子受体（IGF1R）和表皮生长因子受体（EGFR）在子宫内膜癌（EC）中的表达及其与临床病理特征之间的关系。方法采用免疫组化法检测49例正常子宫内膜组织、42例子宫内膜不典型增生组织和156例EC组织中IGF1R和EGFR的表达。收集156例EC患者的临床资料,分析IGF1R和EGFR表达与EC临床病理特征之间的关系。采用Pearson相关分析评估IGF1R与EGFR的相关性。结果EC组织中IGF1R及EGFR的阳性率均明显高于正常子宫内膜组织及不典型增生子宫内膜组织（P＜0.01）。Pearson相关分析结果显示,IGF1R与EGFR呈正相关（r=0.618,P＜0.01）。EC患者中IGF1R高表达与EC的分化、国际妇产科联盟（FIGO）分期、分型、肌层浸润、淋巴结转移、脉管浸润及雌激素受体（ER）表达有关（P＜0.05）,与年龄、孕激素受体（PR）表达无关（P＞0.05）。EGFR高表达与EC的分化、FIGO分期、分型、淋巴结转移有关（P＜0.05）,与年龄、肌层浸润、脉管浸润、ER表达和PR表达无关（P＞0.05）。双指标高表达（IGF1R和EGFR均高表达）组淋巴结转移的阳性率明显高于单指标高表达（IGF1R或EGFR高表达）组和双指标低表达（IGF1R和EGFR均低表达）组（P＜0.05）。结论 IGF1R和EGFR与EC不良的临床病理特征有关,二者联合检测或能用于判断EC淋巴结转移。

环状RNA是一种共价闭合环状分子，在环状RNA微小RNA信使RNA调控轴中充当微小RNA的海绵作用，可调控基因转录及蛋白质翻译。在妇科肿瘤中，环状RNA存在差异性表达，可影响细胞的增殖、迁移、侵袭，从而发挥抑癌或促癌作用。环状RNA