The Hippo pathway is dysregulated in multiple types of human cancer, including ovarian cancer. Nuclear expression of yes-associated protein 1 (YAP1), a downstream transcription coactivator of the Hippo pathway, has been demonstrated to promote tumorigenesis in ovarian cancer and may serve as a poor prognostic indicator. However, transcriptional coactivator with PDZ binding motif (TAZ), a downstream target of the Hippo pathway and paralog of YAP in mammalian cells, has not been fully investigated in ovarian cancer. The present study aimed to investigate the dysregulation and biological function of TAZ in ovarian cancer. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that TAZ mRNA and protein levels, respectively, were upregulated in ovarian cancer, and a meta-analysis of ovarian cancer microarray datasets identified that increased expression of TAZ mRNA is correlated with poor prognosis in patients with ovarian cancer. In addition, TAZ-knockdown in ovarian cancer cells demonstrated that TAZ regulates the migration, proliferation and epithelial-mesenchymal transition of ovarian cancer cells. Furthermore, pharmacological disruption of the YAP/TAZ/TEA domain protein complex resulted in a decrease in ovarian cancer cell migration, proliferation and vimentin expression. The results of the present study indicate that the overexpression of TAZ is important in the development and progression of ovarian cancer, and may function as a potential drug target for treatment of this disease entity.
Of gynecological cancers, cervical cancer has the second highest incidence globally and is a major cause of cancer‑associated mortality in women. An increasing number of studies have reported that microRNAs (miRNAs) have important roles in cervical cancer carcinogenesis and progression through regulation of various critical protein‑coding genes. The aim of the present study was to investigate the expression and biological roles of miRNA‑211 (miR‑211) in cervical cancer and its underlying molecular mechanism. The results of reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) demonstrated that the expression levels of miR‑211 in cervical cancer tissues and cell lines were significantly lower compared with adjacent normal tissues and the normal human cervix epithelial cell line, respectively. Furthermore, upregulation of miR‑211 by transfection with miR‑211 mimics inhibited cell proliferation, migration and invasion of cervical cancer, as determined by MTT, Transwell and Matrigel assays, respectively. Bioinformatics analysis and luciferase reporter assay results indicated that zinc finger E‑box binding homeobox 1 (ZEB1) may be a direct target gene of miR‑211. In addition, RT‑qPCR and western blot analysis results demonstrated that miR‑211 overexpression markedly reduced ZEB1 expression at mRNA and protein levels in cervical cancer. Furthermore, the effects of ZEB1 downregulation on the proliferation, migration and invasion of cervical cancer cells were similar to those induced by miR‑211 overexpression. These results indicate that miR‑211 may act as a tumor suppressor in cervical cancer by directly targeting ZEB1. Therefore, miR‑211/ZEB1‑based targeted therapy may represent a potential novel treatment for patients with cervical cancer.
This study is intended to explore the effect of transcriptional coactivator with PDZ binding motif (TAZ) expression in ovarian cancer cells as well as investigate the expression of signal proteins Smad3 and Snail1. Ovarian cancer cells (SKOV-3) were divided into two groups: control and TAZ overexpression. The overexpression of TAZ in SKOV-3 cells was determined by immunofluorescence, western blot, and qRT-PCR. The proliferation, invasiveness, and expression of epithelial mesenchymal transformation (EMT)-associated proteins were detected, and the expression of Smad3 and Snail1 proteins was determined by qRT-PCR and western blot, respectively. Small interfering RNA (siRNA) targeting TAZ were synthesized and used to transfect SKOV-3. Cell migration and invasion were observed via a wound healing assay and a transwell assay, respectively. The expressions of representative genes involved in proliferation and migration, EMT-associated proteins and Smad3 and Snail1 proteins were also detected by western blot assays. The results of qRT-PCR, immunofluorescence, and western blot showed that, compared with the control group, the expressions of Smad3 and Snail1 protein were upregulated, and the expression of EMT-related genes-including Actin, N-cadherin, and Vimentin protein-was downregulated in the TAZ overexpression group. After TAZ mRNA was suppressed, the migration and invasion ability of the TAZ siRNA group was weaker than that of the control group. In addition, the expression level of Smad3 and Snail1 decreased when TAZ was silenced, while the expression of EMT-related genes increased. Therefore, TAZ in ovarian cancer cells can promote growth, migration, and invasiveness of cancer cells by regulating genes related to proliferation, migration, and invasion.
Background. Ovarian cancer is a fatal gynecological malignancy. The resistance to chemotherapy in ovarian cancer treatment has been a thorny issue. This study is aimed at probing the molecular mechanism of cisplatin (DDP) resistance in ovarian cancer. Methods. Bioinformatics analysis was conducted to examine the role of Nod-like receptor protein 3 (NLRP3) in ovarian cancer. The NLRP3 level in DDP-resistant ovarian cancer tumors and cell lines (SKOV3/DDP and A2780/DDP) was evaluated by applying immunohistochemical staining, western blot, and qRT-PCR. Cell transfection was conducted to regulate the NLRP3 level. Cell abilities to proliferate, migrate, invade, and apoptosis were measured employing colony formation, CCK-8, wound healing, transwell, and TUNEL assays, respectively. Cell cycle analysis was completed via flow cytometry. Corresponding protein expression was measured by western blot. Results. NLRP3 was overexpressed in ovarian cancer, correlated with poor survival, and upregulated in DDP-resistant ovarian cancer tumors and cells. NLRP3 silencing exerted antiproliferative, antimigrative, anti-invasive, and proapoptotic effects in A2780/DDP and SKOV3/DDP cells. Additionally, NLRP3 silencing inactivated NLRPL3 inflammasome and blocked epithelial-mesenchymal transition via enhancing E-cadherin and lowering vimentin, N-cadherin, and fibronectin. Conclusion. NLRP3 was overexpressed in DDP-resistant ovarian cancer. NLRP3 knockdown hindered the malignant process of DDP-resistant ovarian cancer cells, providing a potential target for DPP-based ovarian cancer chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.