Wang Xuejun, He Zirong, Zhao Wenting, Li Lina, Hou Fang
Department of Pediatric Surgery of Children's Medical Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China.
Department of Geriatric Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan Province, China.
Int J Biol Macromol. 2025 Sep;322(Pt 3):146602. doi: 10.1016/j.ijbiomac.2025.146602. Epub 2025 Aug 7.
Long non-coding RNA LINC00467 exerts a significant impact on various cancer types. However, its precise role in non-small-cell lung cancer (NSCLC) is not fully elucidated. Thus, the current study investigated the potential mechanism by which LINC00467 contributes to the progression of NSCLC. RT-qPCR and fluorescence in situ hybridization (FISH) results showed that overexpression of LINC00467 is closely associated with malignant characteristics in NSCLC patients. It promoted NSCLC cell proliferation and metastasis in both cell culture and animal models. Co-immunoprecipitation (Co-IP) and Western blot results indicated that LINC00467 may enhance the proteasome-dependent degradation of PABPC1 by facilitating its interaction with the ubiquitin E3 ligase E4B. Furthermore, LINC00467 was observed to influence the activity of the Wnt/β-catenin signaling pathway, possibly by regulating PABPC1 stability in NSCLC cells. These findings suggest that LINC00467 may contribute to NSCLC progression through a mechanism involving PABPC1, with the potential to modulate the Wnt/β-catenin pathway. This regulatory axis may provide insight into future therapeutic targets for NSCLC.
长链非编码RNA LINC00467对多种癌症类型都有显著影响。然而，其在非小细胞肺癌（NSCLC）中的具体作用尚未完全阐明。因此，本研究探讨了LINC00467促进NSCLC进展的潜在机制。逆转录定量聚合酶链反应（RT-qPCR）和荧光原位杂交（FISH）结果显示，LINC00467的过表达与NSCLC患者的恶性特征密切相关。在细胞培养和动物模型中，它均促进了NSCLC细胞的增殖和转移。免疫共沉淀（Co-IP）和蛋白质免疫印迹结果表明，LINC00467可能通过促进PABPC1与泛素E3连接酶E4B的相互作用，增强蛋白酶体依赖性的PABPC1降解。此外，观察到LINC00467可能通过调节NSCLC细胞中PABPC1的稳定性来影响Wnt/β-连环蛋白信号通路的活性。这些发现表明，LINC00467可能通过涉及PABPC1的机制促进NSCLC进展，并有可能调节Wnt/β-连环蛋白通路。这一调控轴可能为NSCLC未来的治疗靶点提供思路。
