Analysis of the Role and Mechanism of ZEB1 in Regulating Cervical Carcinoma Progression via Modulating PD-1/PD-L1 Checkpoint

Abstract

Background. Cervical carcinoma (CC) is a common and highly malignant tumor in women. The involvement of zinc finger E-box binding homeobox 1 (ZEB1) in many kinds of tumors has been well-documented; however, its role and mechanism in CC remain to be clarified. Objective. This study investigated the mechanism of ZEB1 in modulating the growth and metastasis of CC cells. Methods. The expression of ZEB1 in CC tissues and adjacent normal counterparts was determined by reverse transcription-polymerase chain reaction (RT-PCR). The correlation between ZEB1 and patient clinicopathological indexes was analyzed. In vitro, gain and loss functions of ZEB1 were performed in C-33A and HeLa cell lines. The proliferation, migration, and invasion of CC cells were detected by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The expression levels of apoptosis-related proteins such as BCL2-associated X (Bax), B-cell lymphoma-2 (Bcl2), and Caspase-3, as well as epithelial-mesenchymal transition (EMT)-associated proteins including E-cadherin, Vimentin, and Snail, were measured by Western blotting. In addition, the targeting relationship between ZEB1 and programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) was predicted by bioinformatics and further verified by dual-luciferase reporter assay. Results. ZEB1 was significantly up-regulated in CC tissues compared with normal counterparts. ZEB1 overexpression promoted the migration, proliferation, and invasion of CC cells and inhibited apoptosis, while knocking down ZEB1 contributed to the opposite effects. In addition, experiments on related mechanisms confirmed that ZEB1 targeted the 3’EUTR terminal of PD-1/PD-L1 and negatively regulated its expression. And an interaction between ZEB1 and PD-1/PD-L1 was identified. Conclusion. ZEB1 can promote the proliferation and metastasis of CC cells via modulating the PD-1/PD-L1 checkpoint.

A miRNA-Based Prognostic Model to Trace Thyroid Cancer Recurrence

“…ZEB1 functions to regulate important transcriptional networks necessary for cell differentiation, maintenance, and function [ 67 ]. It can modulate the PD-1/PD-L1 checkpoint [ 68 , 69 ], promote cell proliferation and migration, and inhibit apoptosis [ 70 ]. It also plays a crucial role in the maintenance of cancer stem cells [ 71 ].…”

Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer

“…These targeted proteins and genes play critical roles in cell proliferation, apoptosis, motility, angiogenesis, invasion, and metastasis in thyroid cancer. For example, AKT is vital in the PI3K/Akt signaling pathway [49], ZEB1 modulates the PD-1/PD-L1 checkpoint and cancer stem cell maintenance [50][51][52], ZEB2 triggers epithelial-mesenchymal transition and activates the Wnt/betacatenin pathway [53,54], RAB5C regulates angiogenesis and cell migration [55][56][57], and DUSP6 is involved in thyroid tumorigenesis by regulating the ERK1/2 pathway [58]. Three ncRNAs-TUG1, n384546, and circNUP214-can sponge and suppress miR-145, leading to cancer progression and metastasis [10,11,59].…”

Retracted: Analysis of the Role and Mechanism of ZEB1 in Regulating Cervical Carcinoma Progression via Modulating PD‐1/PD‐L1 Checkpoint

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”