CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase-1-dependent pyroptosis

Sep 24, 2026

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Charged multivesicular body protein 3 (CHMP3), a component of the ESCRT-III complex, is investigated as a tumor susceptibility factor in hepatocellular carcinoma (HCC), where its function remains unclear. Bioinformatics from TCGA data links CHMP3 with pyroptosis. Tissue CHMP3 expression is assessed by immunohistochemistry and western blot. CHMP3 is manipulated in HepG2 and Huh-7 cells using siRNA and overexpression plasmids, followed by assays for proliferation, migration, invasion, and ultrastructural morphology. Caspase-1 pathway proteins are evaluated and a xenograft model tests tumorigenicity in vivo.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Pyroptosis and ESCRT signaling

INTERNATIONAL JOURNAL OF ONCOLOGY 64: 8, 2024 CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase‑1‑dependent pyroptosis YUTING ZHENG 1 , SHAOJIE YANG 1 , WANLIN DAI2 , JINGNAN WANG 1 , SHIYUAN BI 1 , XIAOLIN ZHANG 1 , ZHUYUAN ZHENG 1 , YANG SUN 1 , SHUODONG WU 1 and JING KONG 1 1Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004; 2Innovation Institute of China Medical University, Heping, Shenyang, Liaoning 110122, P.R. China Received June 23, 2023; Accepted October 31, 2023 DOI: 10.3892/ijo.2023.5596 Abstract. Charged multivesicular body protein 3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT) III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocel‑ lular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohis‑ tochemistry and western blot analysis. Subsequently, HepG2 and Huh‑7 cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit‑8 assays. Wound healing and Transwell assays were used to examine the migratory and inva‑ sive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blot‑ ting was used to examine the expression of caspase‑1 signaling pathway related proteins, a classic pathway of pyroptosis. In Correspondence to: Professor Jing Kong, Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping, Shenyang, Liaoning 110004, P.R. China E‑[mail: kongjing1998@163.com](mail: kongjing1998@163.com) Abbreviations: CHMP3, charged multivesicular body protein 3; ESCRT, endosomal sorting complexes required for transport; HCC, hepatocellular carcinoma; DEGs, differentially expressed genes; TCGA, The Cancer Genome Atlas; IL, interleukin; NLRP3, NOD‑like receptor thermal protein domain associated protein 3; GSDMD, Gasdermin D; GEPIA, Gene Expression Profiling Interactive Analysis; HPA, Human Protein Atlas; siRNA: small interfering RNA; PPI, protein‑protein interaction; OS, overall survival; AYC, Ac‑YVAN‑CMK; MMP9, matrix metalloproteinase‑9; TEM, transmission electron microscopy; TNBC, triple‑negative breast cancer Key words: hepatocellular carcinoma, pyroptosis, CHMP3, caspase‑1, proliferation addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 in vivo. The results demon‑ strated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overex‑ pression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh‑7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase‑1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase‑1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase‑1‑mediated pyroptosis pathway. Introduction Hepatocellular carcinoma (HCC) is the 6th ubiquitous tumor worldwide and the main cause of cancer‑related deaths (1) . Previous evidence revealed that after decades of dramatic increasing, the incidence of primary liver cancer in men has stabilized, but the incidence in women continues to rise by >2% per year (2). Recently, there have been novel advances in the therapy of precision management of HCC, such as accurate surgical resection, immunotherapy and targeted

FAQs

What role does CHMP3 have in hepatocellular carcinoma progression?

CHMP3 expression is reported to be upregulated in HCC and associated with poor prognosis, and manipulating CHMP3 alters proliferation, migration, and invasion of liver cancer cells.

How is pyroptosis connected to caspase-1 in this study?

The study links CHMP3 knockdown to activation of the caspase-1-mediated pyroptosis signaling pathway, which can be reversed by the caspase-1 inhibitor AYC.

What experimental approaches are used to test the effects of CHMP3?

CHMP3 expression is examined in tissues by immunohistochemistry and western blot, then altered in HCC cell lines via siRNA or overexpression plasmids. Functional assays include CCK-8 and colony formation for growth, wound healing and Transwell for migration/invasion, transmission electron microscopy for morphology, and a xenograft model for in vivo tumorigenicity.

Sep 24, 2026

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