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该基因在卵巢透明细胞癌中的肿瘤抑制作用。

Tumor Suppressive Role of the Gene in Ovarian Clear Cell Carcinoma.

作者信息

Dozen Ai, Shozu Kanto, Shinkai Norio, Ikawa Noriko, Aoyama Rina, Machino Hidenori, Asada Ken, Yoshida Hiroshi, Kato Tomoyasu, Hamamoto Ryuji, Kaneko Syuzo, Komatsu Masaaki

机构信息

Division of Medical AI Research and Development, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

出版信息

J Pers Med. 2022 Dec 2;12(12):1999. doi: 10.3390/jpm12121999.

Abstract

Ovarian clear cell carcinoma (OCCC) has a poor prognosis, and its therapeutic strategy has not been established. PRELP is a leucine-rich repeat protein in the extracellular matrix of connective tissues. Although PRELP anchors the basement membrane to the connective tissue and is absent in most epithelial cancers, much remains unknown regarding its function as a regulator of ligand-mediated signaling pathways. Here, we obtained sets of differentially expressed genes by PRELP expression using OCCC cell lines. We found that more than 1000 genes were significantly altered by PRELP expression, particularly affecting the expression of a group of genes involved in the PI3K-AKT signaling pathway. Furthermore, we revealed the loss of active histone marks on the loci of the gene in patients with OCCC and how its forced expression inhibited cell proliferation. These findings suggest that PRELP is not only a molecule anchored in connective tissues but is also a signaling molecule acting in a tumor-suppressive manner. It can serve as the basis for early detection and novel therapeutic approaches for OCCC toward precision medicine.

摘要

卵巢透明细胞癌(OCCC)预后较差,其治疗策略尚未确立。PRELP是一种在结缔组织细胞外基质中富含亮氨酸重复序列的蛋白质。尽管PRELP将基底膜锚定到结缔组织,且在大多数上皮癌中不存在,但关于其作为配体介导信号通路调节因子的功能仍有许多未知之处。在此,我们使用OCCC细胞系通过PRELP表达获得了差异表达基因集。我们发现超过1000个基因因PRELP表达而发生显著改变,尤其影响了一组参与PI3K-AKT信号通路的基因的表达。此外,我们揭示了OCCC患者中该基因位点上活性组蛋白标记的缺失以及其强制表达如何抑制细胞增殖。这些发现表明,PRELP不仅是一种锚定在结缔组织中的分子,也是一种以肿瘤抑制方式起作用的信号分子。它可为OCCC的早期检测和精准医学的新型治疗方法奠定基础。

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