RETRACTED: LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8

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, 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.

Cancer Stem Cells in Ovarian Cancer—A Source of Tumor Success and a Challenging Target for Novel Therapies

“…The transfection of CD133+ OCSCs with LINC00115 lncRNA promoted stemness and inhibited apoptosis of OCSCs by up-regulating SOX9 and the Wnt/β-catenin pathway [ 334 ]. In SKOV3 and OVCAR3 cell cultures, the lncRNA T-cell factor-7 (lnc-TCF7) was found to be up-regulated, followed with decreased apoptosis and increased CD44, CD133 expression and CD44+CD133+ cell proportion with concomitant spheres formation efficiency and drug resistance against cisplatin [ 335 ]. In HGOC cell lines (OVCAR3, CAOV3, OVCAR5, COV362, Kuramochi), lncRNA HOTAIR was generally overexpressed, but its expression was especially up-regulated in ALDH+ OCSCs and associated with increased spheroid formation and colony forming ability [ 336 ].…”

Long noncoding RNAs as therapeutic targets to overcome chemoresistance in ovarian cancer

“…LncRNA TCF7 has been found to enhance cell viability, migration, invasion via modulation of ITGB8 in epithelial ovarian cancer ( Su and Huang, 2021 ). Moreover, lncRNA TCF7 promoted the stemness of ovarian cancer cells via acceleration of spheres formation by promotion of CD44 and CD133 expression.…”

“…Moreover, lncRNA TCF7 promoted the stemness of ovarian cancer cells via acceleration of spheres formation by promotion of CD44 and CD133 expression. Furthermore, lncRNA TCF7 accelerated cisplatin resistance in epithelial ovarian cancer cells ( Su and Huang, 2021 ). Molecular experimental data showed that lncRNA TCF7 promoted the expression of ITGB8 and exerted its oncogenic function in ovarian cancer ( Su and Huang, 2021 ).…”

“…Furthermore, lncRNA TCF7 accelerated cisplatin resistance in epithelial ovarian cancer cells ( Su and Huang, 2021 ). Molecular experimental data showed that lncRNA TCF7 promoted the expression of ITGB8 and exerted its oncogenic function in ovarian cancer ( Su and Huang, 2021 ).…”

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

“…Integrin α2, a direct target of miR-206, promotes TNBC self-renewal-related mammosphere formation, where canonical Wnt signaling is involved ( 189 ). Recently, a study demonstrated that upregulation of integrin β8 mediated by lnc-TCF7 leads to ovarian cancer stemness ( 190 ). Integrin αvβ8, a key activator of TGF-β, regulates immunotherapy and radiotherapy resistance, which may be reversed by a potent blocking monoclonal antibody against integrin αvβ8 (ADWA-11) in prostate cancer ( 191 ).…”