前列腺癌（PCa）是第二常见的男性癌症，具有高发生骨转移的倾向。长链非编码RNA（lncRNA）包括TMPO-AS1，在PCa的进展中发挥着关键作用。然而，TMPO-AS1在PCa骨转移（BM）中的功能及其潜在分子机制尚不清楚。在这里，我们发现TMPO-AS1的长转录本（TMPO-AS1L）在具有骨转移的PCa组织中上调，TMPO-AS1L的过表达与进展的临床病理特征和降低的PCa患者无BM生存率相关。上调TMPO-AS1L促进了PCa细胞的体外和体内骨转移能力，而下调TMPO-AS1L则抑制了这种能力。机制上，我们证明TMPO-AS1L作为一个支架，增强了酪氨酸激酶2α1（CSNK2A1）和DEAD-box螺旋丝环酶3-X连锁（DDX3X）的相互作用，并激活了Wnt/β-连位蛋白信号通路，从而促进了PCa的骨转移。此外，PCa中TMPO-AS1L的上调是由由一般转录因子IIF亚单位2（GTF2F2）调节的转录延伸所导致的。综上所述，我们的研究为TMPO-AS1L在PCa骨转移中的作用提供了重要的见解，确定了TMPO-AS1L作为PCa骨转移预后和治疗靶点的候选标志物。© 2023年。细胞死亡和分化协会（ADMC）。

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-AS1L) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1L promoted, whereas downregulated TMPO-AS1L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1L 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-AS1L 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-AS1L in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.© 2023. Cell Death Differentiation Association (ADMC).