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SLFN5 促进卵巢癌中上皮细胞到间充质细胞的可逆转化。

SLFN5 promotes reversible epithelial and mesenchymal transformation in ovarian cancer.

机构信息

Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou, First People's Hospital, Hangzhou, 310006, China.

Westlake Institute for Advanced Study, Zhejiang, Hangzhou, 310024, China.

出版信息

J Ovarian Res. 2023 Feb 6;16(1):33. doi: 10.1186/s13048-023-01103-7.

Abstract

Ovarian cancer is a disease with increasing incidence worldwide, and there is an urgent need for chemotherapy and biological targeted therapy. Epithelial-mesenchymal transformation (EMT) is an important initiation stage for tumor cells to acquire the ability to invade and metastasize. A growing number of findings suggest that human Schlafen family member 5(SLFN5) plays a key role in malignancy. However, the role of SLFN5 in ovarian cancer cells has not been fully elucidated. Samples were collected from patients with ovarian cancer diagnosed in Hangzhou First People's Hospital, and the expression of SLFN5 was detected by fluorescence quantitative PCR. The relationship between SLFN5 expression and the progression and malignancy of ovarian cancer was analyzed by using the expression profile data from the Cancer Genome Atlas (TCGA) database. The mRNA expression levels of SLFN5 related upstream and downstream signaling pathways were studied by fluorescence quantitative PCR. Silencing SLFN5 was performed by siRNA transfection. The expression of SLFN5 and transfer-related proteins was examined by Western blot. Transwell and wound healing experiments investigated the migration and invasion ability of ovarian cancer cells. TCGA database analysis results showed that in the population with high SLFN5 expression, compared with the group with low SLFN5 expression, OS was worse (P = 0.011). SLFN5 silencing had a significant inhibitory effect on EMT and invasion movement of ovarian cancer cells. RT-PCR method was used to detect the mRNA changes of SLFN5 in ovarian cancer tissue and adjacent tissue. It was found that the expression of SLFN5 in ovarian cancer tissue was increased, with a significant difference (P < 0.05). Together, these results suggest that SLFN5 may play a synergistic role in tumorigenesis and development of ovarian cancer cells, providing a potential target for future drug development for the treatment of ovarian cancer.

摘要

卵巢癌是一种全球发病率不断上升的疾病,迫切需要化疗和生物靶向治疗。上皮-间充质转化(EMT)是肿瘤细胞获得侵袭和转移能力的重要起始阶段。越来越多的研究结果表明,人类 Schlafen 家族成员 5(SLFN5)在恶性肿瘤中发挥关键作用。然而,SLFN5 在卵巢癌细胞中的作用尚未完全阐明。本研究收集了杭州第一人民医院诊断为卵巢癌的患者样本,通过荧光定量 PCR 检测 SLFN5 的表达。利用癌症基因组图谱(TCGA)数据库中的表达谱数据,分析 SLFN5 表达与卵巢癌进展和恶性程度的关系。通过荧光定量 PCR 研究 SLFN5 相关上下游信号通路的 mRNA 表达水平。通过 siRNA 转染沉默 SLFN5。通过 Western blot 检测 SLFN5 及其转移相关蛋白的表达。Transwell 和划痕愈合实验研究卵巢癌细胞的迁移和侵袭能力。TCGA 数据库分析结果表明,在 SLFN5 高表达人群中,与 SLFN5 低表达组相比,OS 更差(P = 0.011)。SLFN5 沉默对卵巢癌细胞 EMT 和侵袭运动有显著抑制作用。RT-PCR 方法检测卵巢癌组织和相邻组织中 SLFN5 的 mRNA 变化。结果发现,卵巢癌组织中 SLFN5 的表达增加,差异有统计学意义(P < 0.05)。综上所述,这些结果表明,SLFN5 可能在卵巢癌细胞的发生和发展中发挥协同作用,为未来开发治疗卵巢癌的药物提供了潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f89a/9901157/5cd5798c7ea9/13048_2023_1103_Fig1_HTML.jpg

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