Dysregulation of the SREBP pathway is associated with poor prognosis and serves as a potential biomarker for the diagnosis of hepatocellular carcinoma

Li,Xiaodan; Wang,Yuhan; Liu,Junchi; Gao,Tianmiao; Cao,Lizhi; Yan,Meng; Li,Na

doi:10.3892/mmr.2025.13477

Dysregulation of the SREBP pathway is associated with poor prognosis and serves as a potential biomarker for the diagnosis of hepatocellular carcinoma

Authors:
- Xiaodan Li
- Yuhan Wang
- Junchi Liu
- Tianmiao Gao
- Lizhi Cao
- Meng Yan
- Na Li
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Affiliations: Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China, Scientific Research Department, Shanghai University of Medicine amd Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, School of Medical Technology, Shanghai University of Medicine and Health Sciences, Shanghai 201318, P.R. China, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, P.R. China, Scientific Research Department, Shanghai University of Medicine amd Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China
Published online on: February 26, 2025 https://doi.org/10.3892/mmr.2025.13477
Article Number: 112
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is a severe disease associated with a poor prognosis. The role of aberrant lipid metabolism in the development and progression of HCC necessitates detailed characterization. Sterol regulatory element‑binding proteins (SREBPs), pivotal transcription factors governing lipogenesis, are central to this process. The present study aimed to assess the regulation of HCC by the SREBP signaling pathway, examining the expression levels of genes in this pathway, the clinical implications and its prognostic value using the Kaplan‑Meier method. Pearson's correlation coefficient was used to identify the co‑expression of SREBP pathway genes in HCC. Genomic analysis examined the frequency of TP53 mutations in groups with and without SREBP pathway alterations. In addition, small interfering RNAs targeting genes of the SREBP pathway were transfected into Huh‑7 and HCC‑LM3 cell lines. Subsequently, Cell Counting Kit‑8 and Transwell assays were carried out to evaluate the viability and invasion of these cells. Reverse transcription‑quantitative PCR and western blotting were performed to investigate the expression of TP53 in response to silencing of SREBP pathway genes. Dysregulation of SREBP pathway genes was detected in HCC tissues compared with in normal liver tissues, and predicted a poor prognosis. Silencing these genes reduced the viability and invasion of HCC cells. Furthermore, abnormal SREBP pathway gene expression was associated with poor survival rates, vascular invasion, advanced tumor stage and an increased incidence of TP53 mutations. By contrast, knockdown of SREBP pathway genes decreased mutant TP53 expression at both the mRNA and protein levels in HCC cells. The findings of the present study suggested that SREBP pathway genes could serve as promising prognostic biomarkers for HCC. The combined analysis of individual gene expression levels offers offer novel insights into the pathogenesis and progression of HCC.

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