PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m7G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m7G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m7G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m7G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients.
胰腺导管腺癌是全球范围内最常见的恶性肿瘤之一。早期诊断困难与缺乏有效治疗手段是其预后不良的主要原因。因此，亟需为胰腺导管腺癌患者寻找新的诊疗靶点。m7G甲基化是一种常见的RNA修饰类型，在调控肿瘤发展中起关键作用。然而，m7G调控基因与胰腺导管腺癌进展的相关性尚不明确。通过整合TCGA和GEO数据库中胰腺导管腺癌患者的基因表达及相关临床信息，发现m7G结合蛋白NCBP2在胰腺导管腺癌患者中高表达。更重要的是，NCBP2高表达的胰腺导管腺癌患者预后更差。通过构建稳定敲低和过表达NCBP2的胰腺导管腺癌细胞系进行体内外实验，发现敲低NCBP2显著抑制胰腺导管腺癌细胞增殖，而过表达NCBP2则显著促进细胞生长。机制研究表明，NCBP2通过增强c-JUN的翻译，进而激活MEK/ERK信号通路促进胰腺导管腺癌进展。本研究揭示了m7G阅读蛋白NCBP2通过激活MEK/ERK通路促进胰腺导管腺癌进展，可作为胰腺导管腺癌患者潜在的新型治疗靶点。
The m7G Reader NCBP2 Promotes Pancreatic Cancer Progression by Upregulating MAPK/ERK Signaling
肿瘤(癌症)患者之家