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WW domain-containing transcription regulator protein 1 (WWTR1), also known as TAZ, is a transcriptional co-activator that serves as a key downstream effector of the Hippo signaling pathway [1][2]. It functions by interacting with TEAD transcription factors to regulate genes involved in cell proliferation, survival, and the maintenance of stem cell pluripotency [2][3]. In various cancers, including breast, lung, and liver cancer, WWTR1 is frequently overexpressed, driving tumor progression, metastasis, and resistance to therapy [3]. Additionally, WWTR1 plays a significant role in the development of fibrosis by promoting the activation of myofibroblasts and the deposition of extracellular matrix [5]. Targeting WWTR1 mRNA using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) is an emerging therapeutic approach designed to reduce TAZ protein levels and inhibit its pathological signaling [4]. This strategy is particularly relevant in oncology and fibrotic diseases where direct small-molecule inhibition of the TAZ protein has proven challenging [2][4]. References: [1] UniProt (Q9GZV5); [2] Piccolo et al. (2014) Physiol Rev; [3] Zanconato et al. (2016) Cancer Cell; [4] Ionis Pharmaceuticals Pipeline; [5] Noguchi et al. (2017) Am J Respir Crit Care Med.
RNase H-mediated degradation of mRNA or RNA interference (RNAi) to prevent translation of the TAZ protein [4].
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