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肌动蛋白β样2作为上皮性卵巢癌增殖和迁移的新介质

Actin Beta-Like 2 as a New Mediator of Proliferation and Migration in Epithelial Ovarian Cancer.

作者信息

Topalov Nicole Elisabeth, Mayr Doris, Scherer Clemens, Chelariu-Raicu Anca, Beyer Susanne, Hester Anna, Kraus Fabian, Zheng Mingjun, Kaltofen Till, Kolben Thomas, Burges Alexander, Mahner Sven, Trillsch Fabian, Jeschke Udo, Czogalla Bastian

机构信息

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.

Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

出版信息

Front Oncol. 2021 Sep 23;11:713026. doi: 10.3389/fonc.2021.713026. eCollection 2021.

Abstract

The impact of Actin beta-like 2 (ACTBL2), a novel described actin isoform, on epithelial ovarian cancer (EOC) biology has not been investigated so far. In this study, we analyzed the prognostic and functional significance of ACTBL2 and its regulatory element Nuclear factor of activated T-cells 5 (NFAT5). The expression of ACTBL2 and NFAT5 was examined in tissue microarrays of 156 ovarian cancer patients by immunohistochemistry. Aiming to assess the molecular impact of ACTBL2 on cellular characteristics, functional assays were executed upon siRNA knockdown of and . ACTBL2 expression was identified as an independent negative prognostic factor for overall survival of EOC patients. EOC cell lines showed a significantly increased mRNA and protein level of ACTBL2 compared to the benign control. analyses upon siRNA knockdown of displayed a significantly reduced cellular viability, proliferation and migration. siRNA knockdown of proved a significant molecular interplay by inducing a downregulation of ACTBL2 with a thus resulting concordant alteration in cellular functions, predominantly reflected in a decreased migratory potential of EOC cells. Our results provide significant evidence on the negative prognostic impact of ACTBL2 in EOC, suggesting its crucial importance in ovarian carcinogenesis by modulating cellular motility and proliferation.

摘要

肌动蛋白β样2(ACTBL2)是一种新描述的肌动蛋白异构体,其对上皮性卵巢癌(EOC)生物学的影响迄今尚未得到研究。在本研究中,我们分析了ACTBL2及其调节元件活化T细胞核因子5(NFAT5)的预后和功能意义。通过免疫组织化学检测了156例卵巢癌患者组织芯片中ACTBL2和NFAT5的表达。为了评估ACTBL2对细胞特性的分子影响,在对ACTBL2和NFAT5进行小干扰RNA(siRNA)敲低后进行了功能分析。ACTBL2表达被确定为EOC患者总生存的独立阴性预后因素。与良性对照相比,EOC细胞系中ACTBL2的mRNA和蛋白水平显著升高。对ACTBL2进行siRNA敲低后的分析显示细胞活力、增殖和迁移显著降低。对NFAT5进行siRNA敲低证明了一种显著的分子相互作用,即通过诱导ACTBL2下调从而导致细胞功能的一致改变,主要表现为EOC细胞迁移潜能降低。我们的结果为ACTBL2在EOC中的阴性预后影响提供了重要证据,表明其通过调节细胞运动性和增殖在卵巢癌发生中至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2206/8495414/b1abbbab25b0/fonc-11-713026-g001.jpg

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