<p>TOP2A Promotes Cell Migration, Invasion and Epithelial–Mesenchymal Transition in Cervical Cancer via Activating the PI3K/AKT Signaling</p>

Abstract

Background/Objective: Topoisomerases type IIA (TOP2A) was identified to present with a high-expression pattern in cervical cancer. However, TOP2A role in the progression of cervical cancer remains unknown. Here, we aimed to explore the effect and reveal the underlying mechanism of TOP2A in the migration, invasion and epithelial-mesenchymal transition (EMT) of cervical cancer. Materials and Methods: The expression profiles of TOP2A in 20 paired cervical cancer tissues and the paracancerous normal tissues were detected by using Western blotting assay. Transwell chambers were used to test cell migration and invasion abilities. Cell morphology and the expressions of E-cadherin and N-cadherin were detected to assess cell EMT. LY294002 was used to inhibit the activation of PI3K/AKT signaling. Results: Compared with the paracancerous normal tissues, TOP2A was overexpressed in 85% (17/20) cervical cancer tissues. Repression of TOP2A expression in SiHa cells significantly weakened cell migration and invasion abilities, reduced cell numbers in shuttle shape and increased E-cadherin expression while decreased E-cadherin expression. To the opposite, overexpression of TOP2A in Hela cells induced opposite results. In addition, the expression of p-AKT was increased when TOP2A was overexpressed in Hela cells, and p-AKT expression was decreased when TOP2A was silenced in SiHa cells. Moreover, suppression of the PI3K/AKT signaling with LY294002 treatment apparently rescued TOP2A-mediated promotions in cell migration, invasion and EMT in Hela cells. Conclusion: This study reveals that TOP2A is abnormally overexpressed in cervical cancer tissues, and TOP2A overexpression leads to cell migration, invasion and EMT via activating PI3K/AKT signaling.

Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE

“…Most importantly, over expression of IFIT1 or IFIT3 increased EGFR and AKT expression, which is closely related to the activation of the PI3K pathway (75). TOP2A can also activate the PI3K/AKT signaling pathway leading to cell migration (76), whereas an increased expression of KIF11 inhibited the activation of PI3K/AKT signaling pathway (77). In summary, the potential biomarker genes proposed for SLE diagnosis are closely related to PI3K pathway, and the use of PI3K inhibitors reversed the changes associated with ISG15, OAS1, OASL, and IFIT1 (72,78,79).…”

High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling

“…All four genes showed significantly higher expression in CIN3 as compared to normal biopsies in the current study. Specifically, TOP2A, a promoter of epithelial-mesenchymal transition (EMT), has been associated with increased invasive properties of cancer cells, and has been suggested as a prognostic factor for cervical cancer [ 44 ]. Furthermore, TOP2A combined with CDKN2A mRNA expression showed high sensitivity and specificity for HSIL [ 45 ] in LBC samples.…”

Y-Box Binding Protein-1 Promotes Epithelial-Mesenchymal Transition in Sorafenib-Resistant Hepatocellular Carcinoma Cells

“…Several of these regulators are responsible for genomic integrity. TOP2A, PTTG1 and SMC4 play central roles in chromosome stability and ERCC6 takes part in excision repair, of which dysregulation drives deleterious chromosomal aberrations and thus carcinogenesis [ 39 , 40 , 41 , 42 ]. Moreover, it has been reported that regulation of mRNA stability can govern cancer metastasis [ 43 ].…”