Jiang Chenyang, Xu Dengfei, Feng Hao, Ren Zirui, Li Xiang, Chen Yuming, Yu Jifeng, Cang Shundong
Department of Oncology Henan Key Laboratory for Precision Medicine in Cancer, Henan Provincial People's Hospital, No 7, Weiwu Rd, Zhengzhou, 450003, Henan, China.
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Rd, Zhengzhou, 450003, Henan, China.
Discov Oncol. 2024 Sep 19;15(1):465. doi: 10.1007/s12672-024-01354-w.
The main cause of gastric cancer (GC)-related death is due to malignant cell unregulated distant metastasis and proliferation. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has been shown to play an important role in carcinogenesis and the development of metastasis in several tumors. However, its downstream regulatory mechanism in GC is not well defined. Our study aims to investigate the function and regulatory mechanism of hnRNPA1 in GC. We analyzed the differential expression of hnRNPA1 in gastric cancer and paired adjacent normal tissues in the TCGA database. Kaplan-Meier analysis was employed for survival assessment. The expressions of hnRNPA1 in GC cells were measured by qRT-PCR and Western blot. Transwell assay, CCK8 and colony formation assay were used to detect the effect of hnRNPA1 on the metastasis and proliferation ability of GC cells. Additionally, Western blotting was performed to examine the expression of proteins related to the Wnt/β-catenin signaling pathway as well as epithelial-mesenchymal transition (EMT), while further investigations were carried out to explore potential regulatory mechanisms. The results showed that hnRNPA1 was highly expressed differentially in GC over normal gastric tissue. Knocking down hnRNPA1 inhibited the metastasis and proliferation of human gastric cancer cells. Overexpression of hnRNPA1 significantly enhanced the metastatic potential and proliferative capacity of human GC cells. Further mechanism exploration revealed that knocking down hnRNPA1 inhibited the Wnt/β-catenin signaling pathway and WNT1 inducible signaling pathway protein-2 (WISP2), an activator of the Wnt/β-catenin signaling pathway. Whereas overexpression of hnRNPA1 had the opposite effects. Our results demonstrated that hnRNPA1 promoted metastasis and proliferation of GC cells by activating Wnt/β-catenin signaling pathway via WISP2. hnRNPA1 may serve as a potential biomarker and novel therapeutic targets for GC.
胃癌（GC）相关死亡的主要原因是恶性细胞不受控制的远处转移和增殖。异质性核糖核蛋白A1（hnRNPA1）已被证明在几种肿瘤的致癌作用和转移发展中发挥重要作用。然而，其在GC中的下游调控机制尚不清楚。我们的研究旨在探讨hnRNPA1在GC中的功能和调控机制。我们分析了TCGA数据库中胃癌组织和配对的相邻正常组织中hnRNPA1的差异表达。采用Kaplan-Meier分析进行生存评估。通过qRT-PCR和蛋白质免疫印迹法检测GC细胞中hnRNPA1的表达。使用Transwell实验、CCK8和集落形成实验检测hnRNPA1对GC细胞转移和增殖能力的影响。此外，进行蛋白质免疫印迹法检测与Wnt/β-连环蛋白信号通路以及上皮-间质转化（EMT）相关的蛋白质表达，同时进一步研究以探索潜在的调控机制。结果表明，与正常胃组织相比，hnRNPA1在GC中差异高表达。敲低hnRNPA1可抑制人胃癌细胞的转移和增殖。hnRNPA1的过表达显著增强了人GC细胞的转移潜能和增殖能力。进一步的机制探索表明，敲低hnRNPA1可抑制Wnt/β-连环蛋白信号通路以及Wnt/β-连环蛋白信号通路的激活剂WNT1诱导信号通路蛋白2（WISP2）。而hnRNPA1的过表达则产生相反的效果。我们的结果表明，hnRNPA1通过WISP2激活Wnt/β-连环蛋白信号通路促进GC细胞的转移和增殖。hnRNPA1可能作为GC的潜在生物标志物和新的治疗靶点。
