The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin.
The RNA-binding protein PCBP1 represses lung adenocarcinoma progression by stabilizing DKK1 mRNA and subsequently downregulating β-catenin.
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rna结合蛋白PCBP1通过稳定DKK1 mRNA并随后下调β-catenin来抑制肺腺癌的进展。
DOI：
10.1186/s12967-022-03552-y
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发表时间：
2022-07-30
影响因子：
7.4
通讯作者：
He, Jie
中科院分区：
文献类型：
--
作者：
Zheng, Yujia;Zhou, Zheng;Wei, Ran;Xiao, Chu;Zhang, Hao;Fan, Tao;Zheng, Bo;Li, Chunxiang;He, Jie
polyc -RNA结合蛋白1 （polyc -RNA binding protein 1, PCBP1）作为肿瘤抑制因子和RNA调节因子在人类癌症中下调。在此，我们旨在揭示PCBP1在肺腺癌（LUAD）中的生物学功能。首先，通过The Cancer Genome Atlas （TCGA）项目筛选发现PCBP1是维持LUAD的重要生物标志物，并通过免疫组织化学和qPCR证实。通过菌落形成、CCK8、IncuCyte细胞增殖、伤口愈合和Transwell实验，我们证实PCBP1与LUAD细胞的增殖和迁移密切相关。通过对PCBP1敲低细胞的RNA测序，发现下游基因DKK1。利用western blot、qPCR、RIP、RNA拉下和mRNA稳定性分析进一步研究其潜在机制。我们证实PCBP1在LUAD肿瘤组织中下调。PCBP1的减少促进LUAD在体内外的增殖、迁移和侵袭。在机制上，rna结合蛋白PCBP1通过稳定DKK1 mRNA抑制LUAD。随后，DKK1蛋白表达的降低减轻了对Wnt/β-catenin信号通路的抑制作用。综上所述，这些结果表明PCBP1作为肿瘤抑制基因，抑制LUAD的肿瘤发生。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。我们的发现强调了PCBP1作为一个有希望的治疗靶点的潜力。在线版本包含补充材料，可在10.1186/s12967-022-03552-y获得。
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. The online version contains supplementary material available at 10.1186/s12967-022-03552-y.
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