Lai Keng Po, Cheung Angela, Ho Cheuk Hin, Tam Nathan Yi-Kan, Li Jing Woei, Lin Xiao, Chan Ting Fung, Lee Nikki Pui-Yue, Li Rong
Guanxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, PR China.
Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China.
J Cancer. 2020 Feb 19;11(9):2645-2655. doi: 10.7150/jca.40726. eCollection 2020.
The p70 ribosomal protein S6 kinase 1 (S6K1), a serine/threonine kinase, is commonly overexpressed in a variety of cancers. However, its expression level and functional roles in hepatocellular carcinoma (HCC), which ranks as the third leading cause of cancer-related death worldwide, is still largely unknown. In the current report, we show the and overexpression of S6K1 in HCC. In the functional analysis, we demonstrate that S6K1 is required for the proliferation and colony formation abilities in HCC. By using comparative transcriptomic analysis followed by gene ontology enrichment analysis and Ingenuity Pathway Analysis, we find that the depletion of S6K1 can elevate the expression of a cluster of apoptotic genes, tumor suppressor genes and immune responsive genes. Moreover, the knockdown of S6K1 is predicted to reduce the tumorigenicity of HCC through the regulation of hubs of genes including STAT1, HDAC4, CEBPA and ONECUT1. In conclusion, we demonstrate the oncogenic role of S6K1 in HCC, suggesting the possible use of S6K1 as a therapeutic target for HCC treatment.
p70核糖体蛋白S6激酶1（S6K1）是一种丝氨酸/苏氨酸激酶，在多种癌症中普遍过表达。然而，它在全球癌症相关死亡的第三大主要原因——肝细胞癌（HCC）中的表达水平和功能作用仍 largely未知。在本报告中，我们展示了HCC中S6K1的 和 过表达。在功能分析中，我们证明S6K1是HCC增殖和集落形成能力所必需的。通过使用比较转录组分析，随后进行基因本体富集分析和 Ingenuity 通路分析，我们发现S6K1的缺失可以提高一组凋亡基因、肿瘤抑制基因和免疫反应基因的表达。此外，预测敲低S6K1可通过调节包括STAT1、HDAC4、CEBPA和ONECUT1在内的基因枢纽来降低HCC的致瘤性。总之，我们证明了S6K1在HCC中的致癌作用，表明S6K1可能作为HCC治疗的治疗靶点。 （注：原文中“show the and overexpression of S6K1”有缺失内容）
