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Jianjun Jia,1 Suiqun Guo,2 Dong Zhang,1 Xiaohui Tian,3 Xingmei Xie1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou City, Guangdong Province 510632, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou City, Guangdong Province, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen City, Guangdong Province, People’s Republic of ChinaCorrespondence: Jianjun JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, No. 613, West Huangpu Avenue, Tianhe District, Guangzhou City, Guangdong Province 510632, People’s Republic of ChinaTel +86-20-38688357Email jiajianjun615@sohu.comPurpose: Long non-coding RNAs (lncRNAs) may act as oncogenes in several cancers, including endometrial carcinoma (EC). The purpose of the current study is to investigate the regulatory mechanism of exosomal-lncRNA deleted in lymphocytic leukemia1 (DLEU1) on EC.Methods: The expression levels of lncRNA DLEU1, microRNA-381-3p and E2F Transcription Factor 3 (E2F3) in EC tissues or cells were detected using quantitative reverse transcription–polymerase chain reaction (qRT-PCR). We then analysed the proliferation, migration, and invasion of EC cells by performing the MTT assay, wound healing assay, and transwell invasion assay, respectively. Identification of exosomes was detected using Western blot assay. The uptake of exosomes was detected by a confocal microscope. The effects of exosomes on EC cells were investigated by construction of cell co-culture system. The interactions among DLEU1, miR-381-3p and E2F3 were confirmed using the dual-luciferase reporter (DLR) assay.Results: LncRNA DLEU1 expression was highly up-regulated in EC tissues and cells. Knockdown of DLEU1 inhibited the proliferation, migration, and invasion of EC cells. Exosomes could be uptaken by the ambient EC cells. MiR-381-3p was a target of DLEU1 and was negatively modulated by DLEU1. Overexpression of miR-381-3p suppressed the proliferation, migration, and invasion of EC cells. Additionally, E2F3 was the target gene of miR-381-3p and was negatively modulated by miR-381-3p. Upregulation of miR-381-3p and down-regulation of E2F3 reversed the promoting effect of exosomal DLEU1 on EC cells.Conclusion: Exosomal DLEU1 accelerates the development of EC by regulating the miR-381-3p/E2F3 axis, thus DLEU1 may act as a possible therapeutic target for treating EC.Keywords: endometrial carcinoma, exosomes, lncRNA DLEU1, miR-381-3p, E2F3

Jianjun Jia,1 Xiaomao Li,2 Suiqun Guo,3 Xingmei Xie1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510632, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Jianjun JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of ChinaTel/ Fax +86-020-38688359Email jiajianjun615@sohu.comBackground: Dendritic cells (DCs) are reported to play an important role in activating the anti-tumor immune responses. p38 MAPK14 signaling plays an important role in controlling their activity. Here, we identified that miR-155 suppressed the translation of p38 and impaired the functioning of dendritic cells in endometrial cancer.Methods: HEC1A endometrial cancer cell lines were used for the study which was transfected in the C57BL/6 mice. Murine bone marrow-derived dendritic cells (BMDCs) were isolated from the mice. Target prediction was done by TargetScan which was confirmed by RT-PCR analysis. The protein expression was carried by Western blot analysis. Levels of IL-12 were evaluated by ELISA. Mice injected with HEC1A cells were subjected to tumor challenge study.Results: On screening the binding sites of p38 MAPK14 gene, miR-155 was found to bind the 3ʹUTR directly and blocked its translation. The levels of miR-155 were upregulated in dendritic cells and RAW264.7 cells, miR-155 showed inhibitory effect on expression levels of p38. In dendritic cells, miR-155 was found to regulate the expression of IL-12, also miR-155 inhibitor stimulated the differentiation of Th1 cells in mice induced with endometrial cancer. In dendritic cells, miR-155 inhibited the expression of p38 gene and decreased their ability to interfere in tumor growth.Conclusion: The study concludes suppressive role of miR-155 in the process of dendritic cells mediated anti-tumor immunity, also inhibiting miR-155 provides a novel strategy for countering endometrial cancer.Keywords: miR-155, dendritic cells, p38, IL-12, RAW264.7 cells

Aims and background: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer.Methods: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases.Results: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (PConclusion: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.