Wang Xiao, Kuang Wenbin, Ding Jiayu, Li Jiaxing, Ji Minghui, Chen Weijiao, Shen Hao, Shi Zhongrui, Wang Dawei, Wang Liping, Yang Peng
State Key Laboratory of Natural Medicines of China Pharmaceutical University, Jiangsu Key Laboratory of Drug Design and Optimization of China Pharmaceutical University, Nanjing 210009, China.
Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Cancers (Basel). 2022 Jul 26;14(15):3629. doi: 10.3390/cancers14153629.
Pancreatic adenocarcinoma (PAAD) is a highly aggressive cancer. RNA-binding proteins (RBPs) regulate highly dynamic post-transcriptional processes and perform very important biological functions. Although over 1900 RBPs have been identified, most are considered markers of tumor progression, and further information on their general role in PAAD is not known. Here, we report a bioinformatics analysis that identified five hub RBPs and produced a high-value prognostic model based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Among these, the prognostic signature of the double-stranded RNA binding protein Staufen double-stranded RNA () was identified. Firstly, we found that it is a highly expressed critical regulator of PAAD associated with poor clinical outcomes. Accordingly, the knockdown of led to a profound decrease in PAAD cell growth, migration, and invasion and induced apoptosis of PAAD cells. Furthermore, through multiple omics analyses, we identified the key target genes of : Palladin cytoskeletal associated protein (), Heterogeneous nuclear ribonucleoprotein U (), SERPINE1 mRNA Binding Protein 1 (), and DEAD-box polypeptide 3, X-Linked (). Finally, we found that a high expression level of not only helps PAAD evade the immune response but is also related to chemotherapy drug sensitivity, which implies that could serve as a potential target for combinatorial therapy. These findings uncovered a novel role for in PAAD aggression and resistance, suggesting that it probably represents a novel therapeutic and drug development target.
胰腺腺癌（PAAD）是一种侵袭性很强的癌症。RNA结合蛋白（RBPs）调节高度动态的转录后过程并发挥非常重要的生物学功能。尽管已鉴定出1900多种RBPs，但大多数被认为是肿瘤进展的标志物，关于它们在PAAD中的一般作用的更多信息尚不清楚。在此，我们报告了一项生物信息学分析，该分析鉴定了五个枢纽RBPs，并基于癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据集构建了一个高价值的预后模型。其中，鉴定出了双链RNA结合蛋白Staufen双链RNA（）的预后特征。首先，我们发现它是PAAD的一种高表达关键调节因子，与不良临床结果相关。因此，敲低导致PAAD细胞生长、迁移和侵袭显著减少，并诱导PAAD细胞凋亡。此外，通过多种组学分析，我们确定了的关键靶基因：帕拉丁细胞骨架相关蛋白（）、不均一核核糖核蛋白U（）、丝氨酸蛋白酶抑制剂1 mRNA结合蛋白1（）和X连锁的DEAD盒多肽3（）。最后，我们发现的高表达水平不仅有助于PAAD逃避免疫反应，还与化疗药物敏感性有关，这意味着可作为联合治疗的潜在靶点。这些发现揭示了在PAAD侵袭和耐药中的新作用，表明它可能代表了一个新的治疗和药物开发靶点。
