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Background and Objective <p>Global cancer statistics position HCC as the sixth most common malignancy, with mortality rates placing it third. Notably, stress-induced cytoprotective factor CLU is frequently upregulated in HCC, where it has been mechanistically linked to disease progression. Our previous studies demonstrated that CLU is significantly upregulated in the plasma and neoplastic tissues of HCV-induced HCC patients and HCV core protein-expressing HCC cell lines. Our purpose is to elucidate the function and mechanisms of CLU in HCC, particularly in the context of HCV-associated HCC, while also assessing its potential as a drug target.</p> Methods <p>The relationship between CLU and genes associated with apoptosis and invasion was analyzed using clinical databases (GEPIA). CLU knockdown-induced alterations in apoptosis and invasion were characterized in HCV core protein-expressing HCC cell lines employing multiple experimental approaches including western blotting, flow cytometry, and transwell assays.</p> Results <p>CLU expression was positively correlated with anti-apoptotic and pro-invasive genes in HCC. Significant apoptosis induction was achieved through CLU knockdown, mediated by three key molecular changes: pro-apoptotic genes (BAX, PARP, Caspase3, and Caspase9) were upregulated, the anti-apoptotic gene Bcl2 was downregulated, and AKT phosphorylation was inhibited. Additionally, CLU silencing inhibited cellular invasion by diminishing the expression of matrix metalloproteinase 2 (MMP2), N-cadherin and Vimentin.</p> Conclusions <p>CLU-mediated regulation of apoptosis and invasion pathways emerges as a critical mechanism in HCC progression according to our data. Our findings demonstrated that CLU is a promising therapeutic target for HCV-associated HCC, providing novel perspectives for developing targeted treatments against this aggressive cancer.</p>

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Silencing Clusterin Could Attenuate the Cell Properties of HCV Core Protein-Expressing HCC Cell Line

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Fang Han,
  • Chengjie Cui,
  • Jing Cui,
  • Shuxian Zang,
  • Zhenzhen Zhao,
  • Weiguang Ren,
  • Qingshan Zhang,
  • Lingdi Liu,
  • Shiming Dong,
  • Na Fu,
  • Yuemin Nan

摘要

Background and Objective

Global cancer statistics position HCC as the sixth most common malignancy, with mortality rates placing it third. Notably, stress-induced cytoprotective factor CLU is frequently upregulated in HCC, where it has been mechanistically linked to disease progression. Our previous studies demonstrated that CLU is significantly upregulated in the plasma and neoplastic tissues of HCV-induced HCC patients and HCV core protein-expressing HCC cell lines. Our purpose is to elucidate the function and mechanisms of CLU in HCC, particularly in the context of HCV-associated HCC, while also assessing its potential as a drug target.

Methods

The relationship between CLU and genes associated with apoptosis and invasion was analyzed using clinical databases (GEPIA). CLU knockdown-induced alterations in apoptosis and invasion were characterized in HCV core protein-expressing HCC cell lines employing multiple experimental approaches including western blotting, flow cytometry, and transwell assays.

Results

CLU expression was positively correlated with anti-apoptotic and pro-invasive genes in HCC. Significant apoptosis induction was achieved through CLU knockdown, mediated by three key molecular changes: pro-apoptotic genes (BAX, PARP, Caspase3, and Caspase9) were upregulated, the anti-apoptotic gene Bcl2 was downregulated, and AKT phosphorylation was inhibited. Additionally, CLU silencing inhibited cellular invasion by diminishing the expression of matrix metalloproteinase 2 (MMP2), N-cadherin and Vimentin.

Conclusions

CLU-mediated regulation of apoptosis and invasion pathways emerges as a critical mechanism in HCC progression according to our data. Our findings demonstrated that CLU is a promising therapeutic target for HCV-associated HCC, providing novel perspectives for developing targeted treatments against this aggressive cancer.