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Wang, Min; Yin, Chi; Wu, Zhengquan; Wang, Xinwen; Lin, Qijun; Jiang, Xingyu; Du, Hong; Lang, Chuandong; Peng, Xinsheng; Dai, Yuhu
Cell death discovery, 08/2023, Letnik: 9, Številka: 1Journal Article
The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1's function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1 ) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1 correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1 promoted, whereas downregulated TMPO-AS1 inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1 was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/β-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1 in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1 in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1 as a candidate marker of PCa bone metastasis prognosis and therapeutic target.
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in: SICRIS
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