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下调 TRIM27 表达抑制卵巢癌细胞在体外和体内的增殖。

Downregulation of TRIM27 expression inhibits the proliferation of ovarian cancer cells in vitro and in vivo.

机构信息

Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, P. R. China.

Department of Gynecology, Shandong University School of Medicine, Jinan, Shandong, P. R. China.

出版信息

Lab Invest. 2016 Jan;96(1):37-48. doi: 10.1038/labinvest.2015.132. Epub 2015 Nov 16.

Abstract

TRIM27 (tripartite motif-containing 27) was originally identified as a fusion partner with the RET (REarranged during transfection) proto-oncogene and is highly expressed in various tumor cells and tissues. However, the level of expression and function of TRIM27 in ovarian cancer remain unclear. Here we have measured the expression of TRIM27 in normal ovarian and fallopian tube epithelial cells and in ovarian serous carcinoma cells and correlated TRIM27 expression with clinical and pathological parameters. In addition, we detected the effect of TRIM27 knockdown on proliferation of ovarian cancer cells in cell culture and xenografts. The results demonstrated that TRIM27 was highly expressed in ovarian serous carcinoma cells, and TRIM27 expression was significantly correlated with metastasis and FIGO stage in ovarian serous carcinoma patients. Downregulation of TRIM27 expression suppressed the proliferation of ovarian cancer cells in cell culture and inhibited the growth of xenografts in nude mice. TRIM27 knockdown induced cell cycle arrest and apoptosis in ovarian cancer cells by upregulating the expression of p-P38 and downregulating the expression of p-AKT. Thus the present study suggests that TRIM27 could have important roles as an oncogene during the development of ovarian cancer and could serve as a diagnostic and therapeutic target.

摘要

TRIM27(三结构域含 27 个氨基酸)最初被鉴定为 RET(转染重排)原癌基因的融合伙伴,在各种肿瘤细胞和组织中高度表达。然而,TRIM27 在卵巢癌中的表达和功能水平尚不清楚。在这里,我们测量了 TRIM27 在正常卵巢和输卵管上皮细胞以及卵巢浆液性癌细胞中的表达,并将 TRIM27 表达与临床和病理参数相关联。此外,我们检测了 TRIM27 敲低对卵巢癌细胞在细胞培养和异种移植中的增殖的影响。结果表明,TRIM27 在卵巢浆液性癌细胞中高表达,TRIM27 表达与卵巢浆液性癌患者的转移和 FIGO 分期显著相关。下调 TRIM27 表达抑制了卵巢癌细胞在细胞培养中的增殖,并抑制了裸鼠异种移植中的生长。TRIM27 敲低通过上调 p-P38 的表达和下调 p-AKT 的表达诱导卵巢癌细胞周期停滞和凋亡。因此,本研究表明,TRIM27 可能在卵巢癌的发展过程中作为一种癌基因发挥重要作用,并可能作为一种诊断和治疗靶标。

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