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Fascin1 在高级别浆液性卵巢癌中的表达是一个预后标志物,而 Fascin1 的敲低可抑制卵巢癌细胞的增殖。

Fascin1 expression in high-grade serous ovarian carcinoma is a prognostic marker and knockdown of fascin1 suppresses the proliferation of ovarian cancer cells.

机构信息

Department of Gynecologic Oncology, CHA Gangnam Medical Center, Gangnam-Gu, Seoul 135-907, Republic of Korea.

Clinical Research Institute, CHA University, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 463-712, Republic of Korea.

出版信息

Int J Oncol. 2014 Mar;44(3):637-46. doi: 10.3892/ijo.2013.2232. Epub 2013 Dec 30.

Abstract

Fascin1 (FSCN1) involved in cell motility and filopodia assembly plays important roles in biological processes such as cancer invasion and metastasis of multiple epithelial tumors. High-grade serous ovarian carcinoma (HGSOC) is aggressive and metastatic by acquiring an invasive phenotype and this step requires remodeling of the actin cytoskeleton. Thus, the present study aimed to investigate the expression of fascin1 in HGSOC tissues as well as its clinical significance such as prognostic predictors and its utility of therapeutic target. Fascin1 and β-catenin were evaluated using immunohistochemistry on a tissue microarray of 79 HGSOC. Small interfering RNA (siRNA) approach was used to knock down fascin1 expression in ovarian cancer cell lines to determine whether fascin1 contributes to tumor cell proliferation, migration and invasion. Fascin1 expression levels were determined by western blot analysis after siRNA transfection using two human ovarian cancer cell lines (SKOV3 and OVCAR3). Fascin1 overexpression was significantly correlated with lymph node involvement, distance metastasis and high International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV) (P<0.05). A Kaplan-Meier analysis showed that the fascin1 expression group was significantly associated with poor overall survival (P=0.010). We showed that inactivation of fascin1 by siRNA transfection led to a drop in cell viability, and significantly decreased tumor cell proliferation, migration and invasiveness compared to untransfected cells. We found that fascin1 expression is a potential poor marker of prognosis for patients with HGSOC and knockdown of fascin1 suppresses ovarian cancer cell proliferation and migration, this could be applied for therapeutic targets in ovarian cancer treatment.

摘要

Fascin1(FSCN1)参与细胞运动和丝状伪足的组装,在癌症侵袭和多种上皮肿瘤转移等生物过程中发挥重要作用。高级别浆液性卵巢癌(HGSOC)通过获得侵袭表型而具有侵袭性和转移性,这一步骤需要肌动蛋白细胞骨架的重塑。因此,本研究旨在研究 Fascin1 在 HGSOC 组织中的表达及其临床意义,如预后预测因子及其作为治疗靶点的用途。使用组织微阵列对 79 例 HGSOC 组织进行 Fascin1 和β-连环蛋白的免疫组织化学评估。采用小干扰 RNA(siRNA)方法敲低卵巢癌细胞系中的 Fascin1 表达,以确定 Fascin1 是否有助于肿瘤细胞增殖、迁移和侵袭。使用两种人卵巢癌细胞系(SKOV3 和 OVCAR3)通过 siRNA 转染后,通过 Western blot 分析确定 Fascin1 表达水平。Fascin1 的过表达与淋巴结受累、远处转移和国际妇产科联合会(FIGO)分期(III/IV)高显著相关(P<0.05)。Kaplan-Meier 分析显示,Fascin1 表达组与总生存期不良显著相关(P=0.010)。我们表明,通过 siRNA 转染使 Fascin1 失活导致细胞活力下降,与未转染细胞相比,肿瘤细胞增殖、迁移和侵袭性显著降低。我们发现 Fascin1 表达是 HGSOC 患者预后不良的潜在标志物,下调 Fascin1 抑制卵巢癌细胞增殖和迁移,这可应用于卵巢癌治疗的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b08b/3928475/962fa3052b4c/IJO-44-03-0637-g00.jpg

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