Multiple novel hepatocellular carcinoma signature genes are commonly controlled by the master pluripotency factor OCT4 View Full Text


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Article Info

DATE

2019-12-17

AUTHORS

Chao Ye, Xiaoqian Zhang, Xinyu Chen, Qingyi Cao, Xiaobing Zhang, Yanwen Zhou, Wenxin Li, Liangjie Hong, Haiyang Xie, Xiaoli Liu, Hongcui Cao, Ying-Jie Wang, Bo Kang

ABSTRACT

BackgroundWorldwide, hepatocellular carcinoma (HCC) is a common solid tumor with a poor prognosis. HCC is often due to hepatitis B virus (HBV) infection. As yet, efficacious HCC treatment regimens for late-stage HCC patients are lacking. Therefore, the identification of more specific and sensitive biomarkers for its early diagnosis and treatment remains an urgent need.MethodsTotal RNAs from paired HBV-derived HCC tumors and adjacent peritumor tissues (APTs) were subjected to RNA sequencing (RNA-seq), and differentially expressed genes (DEGs) between HCC tumors and APTs were selected and verified.ResultsWe identified 166 DEGs and found that eight top-ranked and verified DEGs (TK1, CTTN, CEP72, TRIP13, FTH1, FLAD1, CHRM2, AMBP) all contained putative OCT4 binding motifs in their promoter regions. TK1, TRIP13 and OCT4 were found to exhibit concurrent higher expression levels in HCC tumors than in APTs. The mRNA levels of TK1, TRIP13 and OCT4 in a cohort of 384 HCC samples from the TCGA database were all found to be negatively correlated with patient overall survival, relapse-free survival and progression-free survival, underscoring the HCC biomarker status of TK1 and TRIP13 on one hand, and implicating their association with OCT4 on the other hand. Furthermore, OCT4 proteins were found to bind to the promoters of both genes in vitro and in vivo. Knocking out OCT4 in HCC-derived cell lines reduced the expression of TK1 and TRIP13 and significantly decreased their tumorigenicity.ConclusionsUsing RNA-seq, we identified several novel HCC signature genes that may serve as biomarkers for its diagnosis and prognosis. Their common transcriptional regulation by OCT4 suggests key roles in the development of HCC, and indicates that OCT4 may serve as a potential therapeutic target. More... »

PAGES

279-295

References to SciGraph publications

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  • Journal

    TITLE

    Cellular Oncology

    ISSUE

    2

    VOLUME

    43

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s13402-019-00487-3

    DOI

    http://dx.doi.org/10.1007/s13402-019-00487-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1123476244

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31848930


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