Zhang Xia, Liu Cun, Cao Yi, Liu Li, Sun Fusheng, Hou Lin
Department of Biochemistry and Molecular Biology, Basic Medical College, Qingdao University, Qingdao, Shandong Province, China.
Qingdao Blood Center, Qingdao, Shandong Province, China.
Pediatr Res. 2025 Jan;97(1):202-212. doi: 10.1038/s41390-022-02073-0. Epub 2022 May 6.
RRS1 plays an important role in regulating ribosome biogenesis. Recently, RRS1 has emerged as an oncoprotein involved in tumorigenicity of some cancers. However its role in neuroblastoma remains unknown.
RRS1 expression was detected in pediatric neuroblastoma patients' tissues and cell lines. The effects of RRS1 knockdown on proliferation, apoptosis, and cell cycle were evaluated in neuroblastoma cell lines. RRS1-related survival pathway was analyzed by co-immunoprecipitation (Co-IP), mass spectrometry, reverse transcription-quantitative real-time PCR (RT-qPCR), and western blot. Protein-protein interaction (PPI) network was constructed using Cytoscape software and the STRING databases.
Increased RRS1 level was found in neuroblastoma cases (35.6%) and cell lines. High RRS1 expression levels were associated with poor prognosis. RRS1 knockdown inhibited cell proliferation, induced apoptosis, and caused cell cycle arrest in SK-N-AS and SH-SY5Y cells. Co-IP and mass spectrometry analysis showed that RRS1 affects PI3K/Akt and nuclear factor κB (NF-κB) pathways. RT-qPCR and western blot results revealed that RRS1 knockdown inhibited the PI3K/Akt/NF-κB pathway through dephosphorylation of key proteins. In PPI network, AKT, PI3K, and P65 connected RRS1 with differentially expressed proteins more closely.
This study suggests RRS1 knockdown may inhibit neuroblastoma cell proliferation by the PI3K/Akt/NF-κB pathway. Therefore, RRS1 may be a potential target for neuroblastoma treatment.
RRS1 is involved in the progression of neuroblastoma. Knockdown of RRS1 contributes to inhibit the survival of neuroblastoma cells. RRS1 is associated with the PI3K/Akt/NF-κB signaling pathway in neuroblastoma cells. RRS1 may be a promising target for neuroblastoma therapy.
RRS1在调节核糖体生物合成中起重要作用。最近，RRS1已成为一种参与某些癌症致瘤性的癌蛋白。然而，其在神经母细胞瘤中的作用仍不清楚。
检测小儿神经母细胞瘤患者组织和细胞系中RRS1的表达。评估RRS1敲低对神经母细胞瘤细胞系增殖、凋亡和细胞周期的影响。通过免疫共沉淀（Co-IP）、质谱分析、逆转录定量实时PCR（RT-qPCR）和蛋白质印迹法分析RRS1相关的生存途径。使用Cytoscape软件和STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络。
在神经母细胞瘤病例（35.6%）和细胞系中发现RRS1水平升高。RRS1高表达水平与预后不良相关。RRS1敲低抑制了SK-N-AS和SH-SY5Y细胞的增殖，诱导了凋亡，并导致细胞周期停滞。Co-IP和质谱分析表明，RRS1影响PI3K/Akt和核因子κB（NF-κB）途径。RT-qPCR和蛋白质印迹结果显示，RRS1敲低通过关键蛋白的去磷酸化抑制PI3K/Akt/NF-κB途径。在PPI网络中，AKT、PI3K和P65将RRS1与差异表达蛋白更紧密地连接起来。
本研究表明，RRS1敲低可能通过PI3K/Akt/NF-κB途径抑制神经母细胞瘤细胞增殖。因此，RRS1可能是神经母细胞瘤治疗的潜在靶点。
RRS1参与神经母细胞瘤的进展。敲低RRS1有助于抑制神经母细胞瘤细胞的存活。RRS1与神经母细胞瘤细胞中的PI3K/Akt/NF-κB信号通路相关。RRS1可能是神经母细胞瘤治疗的一个有前景的靶点。
