Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, P.R. China.
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, P.R. China.
J Exp Clin Cancer Res. 2021 Jan 26;40(1):44. doi: 10.1186/s13046-021-01846-5.
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.
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.
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.
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.
转录共激活因子含有 PDZ 结合基序（TAZ）已被报道参与肿瘤进展、血管生成、上皮-间质转化（EMT）、糖代谢调节和活性氧（ROS）的积累。在此，研究人员发现了 TAZ 在膀胱癌中诱导生物学效应的潜在分子机制。
使用 qRT-PCR、western blot 和免疫组化来确定膀胱癌细胞和组织中的 TAZ 水平。CCK-8、集落形成、管形成、划痕愈合和 Transwell 检测以及流式细胞术用于评估 TAZ、miR-942-3p 和生长停滞特异性基因 1（GAS1）的生物学功能。使用 qRT-PCR 和 western blot 来确定相关基因的表达水平。使用染色质免疫沉淀和双荧光素酶报告基因检测来证实 TAZ 和 miR-942 之间的相互作用。还进行了体内肿瘤发生和比色糖酵解测定。
研究人员证实了 TAZ 在膀胱癌中的上调和重要作用。TAZ 诱导的 miR-942-3p 表达上调通过抑制 TAZ 抑制剂大肿瘤抑制因子 2（LATS2）的表达放大了上游信号。miR-942-3p 减弱了 TAZ 敲低对细胞增殖、血管生成、EMT、糖酵解和 ROS 水平的影响。此外，miR-942-3p 抑制 GAS1 的表达来调节生物学行为。
该研究确定了 TAZ 和 miR-942-3p 之间的一个新的正反馈回路，该回路通过 GAS1 表达调节膀胱癌细胞的生物学功能，并表明 TAZ、miR-942-3p 和 GAS1 可能是膀胱癌治疗的潜在治疗靶点。
