2. Academic Validation
  3. STC2 is a potential biomarker of hepatocellular carcinoma with its expression being upregulated in Nrf1α-deficient cells, but downregulated in Nrf2-deficient cells

STC2 is a potential biomarker of hepatocellular carcinoma with its expression being upregulated in Nrf1α-deficient cells, but downregulated in Nrf2-deficient cells

  • Int J Biol Macromol. 2023 Oct 20:127575. doi: 10.1016/j.ijbiomac.2023.127575.
Qiqi Bu 1,  Yangxu Deng 2,  Qing Wang 2,  Rongzhen Deng 2,  Shaofan Hu 2,  Zhigang Pei 3,  Yiguo Zhang 4
Affiliations

Affiliations

  • 1 Bioengineering College, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China; Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China; The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
  • 2 Bioengineering College, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China; The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
  • 3 Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China.
  • 4 Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China; The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China. Electronic address: [email protected].
PMID: 37866563 DOI: 10.1016/j.ijbiomac.2023.127575
Abstract

Nrf1 (encoded by Nfe2l1) and Nrf2 (encoded by Nfe2l2), as two key members of the CNC-bZIP transcription factor, exhibit significant functional differences in their pathophysiology. Our previous findings demonstrated that loss of Nrf1α (i.e., a full-length isoform of Nrf1) promotes HepG2-derived tumor growth in xenograft mice, but malgrowth of the xenograft tumor is significantly suppressed by knockout of Nrf2. To gain insights into the mechanism underlying such marked distinctions in their pathologic phenotypes, we mined transcriptome data from liver Cancer in the TCGA database to establish a prognostic model and calculate predicted risk scores for each cell line. The results revealed that knockout of Nrf1α markedly increased the risk score in HepG2 cells, whereas the risk score was reduced by knockout of Nrf2. Notably, stanniocalcin 2 (STC2), a biomarker associated with liver Cancer, that is upexpressed in hepatocellular carcinoma (HCC) tissues with a reduction in the overall survival ratio of those patients. We observed increased expression levels of STC2 in Nrf1α-/- cells but decreased expression in Nrf2-/- cells. These findings suggested that STC2 may play a role in mediating the distinction between Nrf1α-/- and Nrf2-/-. Such potential function of STC2 was further corroborated through a series of experiments combined with transcriptomic sequencing. The results revealed that STC2 functions as a dominant tumor-promoter, because the STC2-leading increases in clonogenicity of hepatoma cells and malgrowth of relevant xenograft tumor were almost completely abolished in STC2-/- cells. Together, these demonstrate that STC2 could be paved as a potential therapeutic target, albeit as a diagnostic marker, for HCC.

Keywords

Hepatocellular carcinoma; Nrf1α; Nrf2; Prognostic model; STC2.

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