Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J Transl Med. 2022 Jul 30;20(1):343. doi: 10.1186/s12967-022-03552-y.
PolyC-RNA-binding protein 1 (PCBP1) functions as a tumour suppressor and RNA regulator that is downregulated in human cancers. Here, we aimed to reveal the biological function of PCBP1 in lung adenocarcinoma (LUAD).
First, PCBP1 was identified as an important biomarker that maintains LUAD through The Cancer Genome Atlas (TCGA) project screening and confirmed by immunohistochemistry and qPCR. Via colony formation, CCK8, IncuCyte cell proliferation, wound healing and Transwell assays, we confirmed that PCBP1 was closely related to the proliferation and migration of LUAD cells. The downstream gene DKK1 was discovered by RNA sequencing of PCBP1 knockdown cells. The underlying mechanisms were further investigated using western blot, qPCR, RIP, RNA pulldown and mRNA stability assays.
We demonstrate that PCBP1 is downregulated in LUAD tumour tissues. The reduction in PCBP1 promotes the proliferation, migration and invasion of LUAD in vitro and in vivo. Mechanistically, the RNA-binding protein PCBP1 represses LUAD by stabilizing DKK1 mRNA. Subsequently, decreased expression of the DKK1 protein relieves the inhibitory effect on the Wnt/β-catenin signalling pathway. Taken together, these results show that PCBP1 acts as a tumour suppressor gene, inhibiting the tumorigenesis of LUAD.
We found that PCBP1 inhibits LUAD development by upregulating DKK1 to inactivate the Wnt/β-catenin pathway. Our findings highlight the potential of PCBP1 as a promising therapeutic target.
多聚 C 结合蛋白 1（PCBP1）作为一种肿瘤抑制因子和 RNA 调节剂，在人类癌症中下调。在这里，我们旨在揭示 PCBP1 在肺腺癌（LUAD）中的生物学功能。
首先，通过癌症基因组图谱（TCGA）项目筛选鉴定 PCBP1 是维持 LUAD 的重要生物标志物，并通过免疫组化和 qPCR 进行验证。通过集落形成、CCK8、IncuCyte 细胞增殖、划痕愈合和 Transwell 测定，我们证实 PCBP1 与 LUAD 细胞的增殖和迁移密切相关。通过 PCBP1 敲低细胞的 RNA 测序发现下游基因 DKK1。通过 Western blot、qPCR、RIP、RNA 下拉和 mRNA 稳定性测定进一步研究了潜在机制。
我们证明 PCBP1 在 LUAD 肿瘤组织中下调。PCBP1 的减少促进了 LUAD 在体外和体内的增殖、迁移和侵袭。在机制上，RNA 结合蛋白 PCBP1 通过稳定 DKK1 mRNA 来抑制 LUAD。随后，DKK1 蛋白表达降低缓解了对 Wnt/β-catenin 信号通路的抑制作用。总之，这些结果表明 PCBP1 作为一种肿瘤抑制基因，通过上调 DKK1 抑制 LUAD 的发生。
我们发现 PCBP1 通过上调 DKK1 使 Wnt/β-catenin 通路失活来抑制 LUAD 的发展。我们的研究结果突出了 PCBP1 作为一种有前途的治疗靶点的潜力。
