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长链非编码RNA TCF7通过调控整合素β8促进上皮性卵巢癌的生存能力、迁移能力和干性。

LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness Regulating ITGB8.

作者信息

Su Changlei, Huang Kejin

机构信息

Department of General Surgery, The Second Hospital of Harbin Medical University, Harbin, China.

Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, China.

出版信息

Front Oncol. 2021 Nov 17;11:649655. doi: 10.3389/fonc.2021.649655. eCollection 2021.

Abstract

This study aimed to investigate the carcinogenic role of long non-coding RNA T-cell factor 7 (lnc-TCF7) in epithelial ovarian cancer (EOC). Lnc-TCF7 overexpression and shRNA plasmids were transfected into SKOV3 and OVCAR3 cells, followed by measurement of cell proliferation, migration, invasion, apoptosis, stemness, and mRNA profile (via microarray). Besides, lnc-TCF7 expression was measured in tumor and adjacent tissues from 76 EOC patients. Lnc-TCF7 was upregulated in EOC cell lines; its overexpression increased cell proliferation, migration, invasion, but decreased apoptosis and promoted CD44, CD133 expressions, CD44CD133 cell proportion, spheres formation efficiency and drug resistance to cisplatin in SKOV3 and OVCAR3 cells. Besides, lnc-TCF7 ShRNA exhibited opposite effects comparing with its overexpression. Microarray analysis revealed 267 mRNAs were modulated by lnc-TCF7 dysregulation, among which ITGB8 was the most dysregulated one, which was validated by subsequent western blot and RT-qPCR. Furthermore, ITGB8 overexpression not only induced proliferation, migration, invasion and stemness, but also attenuated the effect of lnc-TCF7 ShRNA on these functions in SKOV3 and OVCAR3 cells. In addition, lnc-TCF7 was upregulated in tumor tissues and correlated with higher pathological grade, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and worse overall survival in EOC patients. Conclusively, lnc-TCF7 regulates multiple oncogenic pathways, promotes proliferation, migration, invasion, stemness upregulating ITGB8. It also correlates with advanced tumor features and poor prognosis in EOC, implying its potential as a target for EOC treatment.

摘要

本研究旨在探讨长链非编码RNA T细胞因子7(lnc-TCF7)在上皮性卵巢癌(EOC)中的致癌作用。将lnc-TCF7过表达质粒和shRNA质粒转染至SKOV3和OVCAR3细胞中,随后检测细胞增殖、迁移、侵袭、凋亡、干性及mRNA谱(通过微阵列)。此外,检测了76例EOC患者肿瘤组织及癌旁组织中lnc-TCF7的表达。lnc-TCF7在EOC细胞系中上调;其过表达增加了细胞增殖、迁移、侵袭,但降低了凋亡,并促进了SKOV3和OVCAR3细胞中CD44、CD133的表达、CD44CD133细胞比例、球体形成效率及对顺铂的耐药性。此外,lnc-TCF7 ShRNA与其过表达表现出相反的作用。微阵列分析显示,267个mRNA受lnc-TCF7失调调控,其中ITGB8失调最为明显,随后的蛋白质免疫印迹和逆转录定量聚合酶链反应验证了这一点。此外,ITGB8过表达不仅诱导了增殖、迁移、侵袭和干性,还减弱了lnc-TCF7 ShRNA对SKOV3和OVCAR3细胞这些功能的影响。此外,lnc-TCF7在肿瘤组织中上调,且与EOC患者更高的病理分级、肿瘤大小、国际妇产科联盟(FIGO)分期及更差的总生存期相关。总之,lnc-TCF7通过上调ITGB8调节多种致癌途径,促进增殖、迁移、侵袭和干性。它还与EOC的晚期肿瘤特征和不良预后相关,暗示其作为EOC治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bb1/8635800/10da4be81a6c/fonc-11-649655-g001.jpg

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