J Cancer 2020; 11(9):2645-2655. doi:10.7150/jca.40726 This issue

Research Paper

Transcriptomic analysis reveals the oncogenic role of S6K1 in hepatocellular carcinoma

Keng Po Lai1,2✉, Angela Cheung2, Cheuk Hin Ho2, Nathan Yi-Kan Tam2, Jing Woei Li2, Xiao Lin3, Ting Fung Chan3,4, Nikki Pui-Yue Lee5, Rong Li1

1. Guanxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, PR China;
2. Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China;
3. School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China;
4. State Key Laboratory of Agrobiotechnology, Chinese University of Hong Kong, Hong Kong SAR, China;
5. Department of Surgery, University of Hong Kong, Hong Kong SAR, China.

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Citation:
Lai KP, Cheung A, Ho CH, Tam NYK, Li JW, Lin X, Chan TF, Lee NPY, Li R. Transcriptomic analysis reveals the oncogenic role of S6K1 in hepatocellular carcinoma. J Cancer 2020; 11(9):2645-2655. doi:10.7150/jca.40726. Available from https://www.jcancer.org/v11p2645.htm

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Abstract

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 in vivo and in vitro 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.

Keywords: S6K1, hepatocellular carcinoma, proliferation, tumorigenicity, transcriptome