A positive feedback loop between TAZ and miR-942-3p modulates proliferation, angiogenesis, epithelial-mesenchymal transition process, glycometabolism and ROS homeostasis in human bladder cancer

Abstract

Background Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. Methods qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. Results We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. Conclusion Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

Immune-Related Nine-MicroRNA Signature for Predicting the Prognosis of Gastric Cancer

“…MiR-942-3p promotes breast cancer progression by downregulating the expression of forkhead box protein A2 ( Zhang J. et al, 2019 ). A new positive-feedback loop was identified between miR-942-3p and a transcriptional coactivator with a PDZ-binding motif, which regulated the biological function of bladder cancer cells and illustrated that these targets might have therapeutic potential as targets for prostate cancer treatment ( Wang et al, 2021 ). The results of that study also suggest that miR-942-3p regulates the development of a variety of tumors.…”

Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer

“…Other in vitro experiments, such as CCK-8 assay, H&E staining, and IHC, have been previously described by us (Wang et al, 2020a(Wang et al, , 2021.…”

ISLR affects colon cancer progression by regulating the epithelial–mesenchymal transition signaling pathway

“…Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the downstream effectors of the Hippo pathway [ 27 ]. Studies have demonstrated the regulatory roles of YAP and TAZ in the EMT process [ 28 , 29 ]. The results showed that the levels of p-YAP and p-TAZ were markedly increased by ISLR silence while decreased by ISLR overexpression (Fig.…”