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Identification of acetyl-CoA carboxylase alpha as a prognostic and targeted candidate for hepatocellular carcinoma

  • RESEARCH ARTICLE
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Abstract

Purpose

The de novo lipogenesis has been a longstanding observation in hepatocellular carcinoma (HCC). However, the prognostic value and carcinogenic roles of the enzyme Acetyl-CoA carboxylase alpha (ACACA) in HCC remains unknown.

Methods

The proteins with remarkable prognostic significance were screened out from The Cancer Proteome Atlas Portal (TCPA) database. Furthermore, the expression characteristics and prognostic value of ACACA were evaluated in multiple databases and the local HCC cohort. The loss-of-function assays were performed to uncover the potential roles of ACACA in steering malignant behaviors of HCC cells. The underlying mechanisms were conjectured by bioinformatics and validated in HCC cell lines.

Results

ACACA was identified as a crucial factor of HCC prognosis. Bioinformatics analyses showed that HCC patients with higher expression of ACACA protein or mRNA levels had poor prognosis. Knockdown of ACACA remarkably crippled the proliferation, colony formation, migration, invasion, epithelial−mesenchymal transition (EMT) process of HCC cells and induced the cell cycle arrest. Mechanistically, ACACA might facilitate the malignant phenotypes of HCC through aberrant activation of Wnt/β-catenin signaling pathway. In addition, ACACA expression was associated with the dilute infiltration of immune cells including plasmacytoid DC (pDC) and cytotoxic cells by utilization of relevant database analysis.

Conclusion

ACACA could be a potential biomarker and molecular target for HCC.

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Availability of data and materials

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

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Funding

This study was supported by grants from National Natural Science Foundation (82070622, 82272839, 81702419), the Key Research and Development Plan of Jiangsu Province (BE2020668), and Science project of Nantong City (JCZ21041).

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Author notes

  1. Yiping Shen, Xin Wang, and Zhiyu Ni have contributed equally to this study.

Authors and Affiliations

  1. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China

    Yiping Shen, Xin Wang, Zhiyu Ni, Shiyu Xu, Shi Qiu & Wenjie Zheng

  2. Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China

    Xin Wang, Shi Qiu, Wenjie Zheng & Jie Zhang

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  1. Yiping Shen
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Contributions

WZ and JZ designed and supervised this study. YS, ZN, and SX conducted the experiments. YS drafted the manuscript. JZ and WZ performed the revision. XW and SQ performed the bioinformatics and statistics. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Wenjie Zheng or Jie Zhang.

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The authors declare that they have no conflict of interest.

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The studies involving human participants were reviewed and approved by the Ethics Committee of Affiliated Hospital of Nantong University (2022-L092).  

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Informed consent was obtained from all individual participants included in the study.

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Shen, Y., Wang, X., Ni, Z. et al. Identification of acetyl-CoA carboxylase alpha as a prognostic and targeted candidate for hepatocellular carcinoma. Clin Transl Oncol 25, 2499–2513 (2023). https://doi.org/10.1007/s12094-023-03137-1

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  • DOI: https://doi.org/10.1007/s12094-023-03137-1

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