Shen Cong, Cao Ruican, Zhou Qiao, Zhou Tao, Wu Tiantian, Gao Wenxin, Wang Gaigai, Feng Guannan, Qiao Longwei, Wang Ting
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School of Nanjing Medical University, Suzhou, China.
Department of Reproduction, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Oncogene. 2025 Jul 22. doi: 10.1038/s41388-025-03500-2.
Ovarian cancer (OC) remains a significant challenge in oncology due to its late diagnosis and poor prognosis. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in cancer biology. Herein, we reported that LINC00654 was highly expressed in OC tissues and correlated with poor patient prognosis. In addition, LINC00654 silencing restrained OC cell proliferation and migration in vitro and in vivo. Mechanically, LINC00654 was identified to directly interact with Human antigen R (HuR), a known RNA-binding protein, through RNA pull-down, RNA immunoprecipitation (RIP), and cross‑linking immunoprecipitation (CLIP). Further analysis revealed that LINC00654 could induce the translocation of HuR from the nucleus to the cytosol, where it regulated the stability of its target oncogenes, such as VASH2. The stabilization of VASH2 subsequently activated the TGF-β pathway, which is known to play a critical role in cancer progression. Taken together, these findings establish a specific mechanism by which LINC00654 interacts with HuR, facilitates its nuclear export, and stabilizes VASH2, thereby activating the TGF-β pathway and promoting OC progression. This insight into LINC00654's role in OC provides potential therapeutic targets for intervention.
由于卵巢癌（OC）诊断较晚且预后较差，它仍然是肿瘤学领域的一项重大挑战。新出现的证据表明，长链非编码RNA（lncRNAs）在癌症生物学中发挥着关键作用。在此，我们报告LINC00654在OC组织中高表达，并与患者的不良预后相关。此外，LINC00654沉默在体外和体内均抑制了OC细胞的增殖和迁移。从机制上来说，通过RNA下拉、RNA免疫沉淀（RIP）和交联免疫沉淀（CLIP），确定LINC00654与已知的RNA结合蛋白人抗原R（HuR）直接相互作用。进一步分析表明，LINC00654可诱导HuR从细胞核转运至细胞质，在细胞质中它调节其靶癌基因（如VASH2）的稳定性。VASH2的稳定随后激活了TGF-β通路，已知该通路在癌症进展中起关键作用。综上所述，这些发现建立了一种特定机制，通过该机制LINC00654与HuR相互作用，促进其核输出，并稳定VASH2，从而激活TGF-β通路并促进OC进展。对LINC00654在OC中作用的这一深入了解为干预提供了潜在的治疗靶点。
