Table_2_LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8.docx

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, CD44+CD133+ 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 via upregulating ITGB8. It also correlates with advanced tumor features and poor prognosis in EOC, implying its potential as a target for EOC treatment.

本研究旨在探讨长非编码RNA T细胞因子7（lnc-TCF7）在上皮性卵巢癌（EOC）中的致癌作用。通过将过表达lnc-TCF7及shRNA质粒转染至SKOV3和OVCAR3细胞中，随后对其细胞增殖、迁移、侵袭、凋亡、干性和mRNA表达谱（通过微阵列分析）进行测量。此外，对76例EOC患者的肿瘤及邻近组织中的lnc-TCF7表达进行了检测。在EOC细胞系中，lnc-TCF7的表达上调；其过表达增加了细胞增殖、迁移、侵袭，并减少了凋亡，同时促进了CD44、CD133的表达，增加了CD44+CD133+细胞的比例，提高了球状体形成效率，并增强了SKOV3和OVCAR3细胞对顺铂的耐药性。此外，与过表达相比，lnc-TCF7的ShRNA表现出相反的效果。微阵列分析揭示了267个mRNA受到lnc-TCF7失调的调控，其中ITGB8的失调最为显著，这一结果随后通过Western blot和RT-qPCR得到了验证。此外，ITGB8的过表达不仅诱导了增殖、迁移、侵袭和干性，还减弱了lnc-TCF7 ShRNA对这些功能在SKOV3和OVCAR3细胞中的抑制作用。此外，lnc-TCF7在肿瘤组织中表达上调，与更高的病理分级、肿瘤大小、国际妇科和产科联盟（FIGO）分期以及EOC患者的较差总生存率相关。综上所述，lnc-TCF7通过上调ITGB8调节多个致癌通路，促进增殖、迁移、侵袭和干性，并与EOC的肿瘤特征和不良预后相关，暗示其作为EOC治疗靶点的潜力。