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.
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.
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TAZ 和 miR-942-3p 之间的正反馈环调节人膀胱癌的增殖、血管生成、上皮-间质转化过程、糖代谢和 ROS 稳态
DOI：
10.1186/s13046-021-01846-5
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发表时间：
2021-01-26
期刊：
影响因子：
--
通讯作者：
Jin X
中科院分区：
文献类型：
--
作者：
Wang F;Fan M;Zhou X;Yu Y;Cai Y;Wu H;Zhang Y;Liu J;Huang S;He N;Hu Z;Ding G;Jin X
具有PDZ结合基序的转录辅激活因子（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）积累。在此，发现了TAZ诱导膀胱癌生物学效应的潜在分子机制。采用qRT-PCR、Western blotting和免疫组化方法检测膀胱癌细胞和组织中TAZ的表达水平。采用CCK-8、集落形成、管形成、伤口愈合、Transwell实验和流式细胞术等方法评价TAZ、miR-942- 3 p和生长抑制特异性蛋白1（GAS 1）的生物学功能。采用QRT-PCR和western blotting检测相关基因的表达水平。进行染色质免疫沉淀和双荧光素酶报告基因测定以确认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。我们证实了TAZ在膀胱癌中的上调和重要作用。TAZ诱导的miR-942- 3 p表达上调通过抑制大肿瘤抑制因子2（LATS 2，TAZ抑制剂）的表达来放大上游信号传导。MiR-942- 3 p减弱了TAZ敲减对细胞增殖、血管生成、EMT、糖酵解和ROS水平的影响。此外，miR-942- 3 p抑制GAS 1的表达，从而调节其生物学行为。我们的研究确定了TAZ和miR-942- 3 p之间的一种新的正反馈环，该环通过GAS 1表达调节膀胱癌细胞的生物学功能，并说明TAZ，miR-942- 3 p和GAS 1可能是膀胱癌治疗的潜在治疗靶点。在线版本包含补充材料，可通过10.1186/s13046-021-01846-5获取。
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. The online version contains supplementary material available at 10.1186/s13046-021-01846-5.
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