Function and mechanism of suppressor of zeste 12 in hepatocellular carcinoma

doi:10.3969/j.issn.1674-8115.2025.09.006

Abstract

Abstract:

Objective ·To explore the function and potential mechanism of suppressor of zeste 12 (SUZ12) in hepatocellular carcinoma (HCC). Methods ·The expression of SUZ12 in HCC patients was analyzed using R language in liver cancer datasets, and relevant survival curves were drawn. Stable knockdown of SUZ12 was established in the liver cancer cell lines LM3 and Huh7. The knockdown efficiency of SUZ12 was assessed using quantitative real-time PCR (qPCR) and Western blotting. Cell proliferation ability was assessed using CCK-8 assay and colony formation assay. Using the hydrodynamic tail vein injection (HTVI) method, Suz12 was knocked out in the livers of fully immunocompetent mice to explore its tumorigenic function in vivo. The molecular mechanism of SUZ12 regulating HCC was explored using The Cancer Genome Atlas (TCGA) database. R language was used to analyze the relationship between SUZ12 and the expression of cancer stem cell (CSC) markers as well as key glycolysis-related genes. Findings were validated in liver cancer cell lines and mouse tumor tissues. Results ·The expression of SUZ12 in liver cancer tissues was higher than in adjacent non-tumor tissues, and its expression increased with higher tumor stage. HCC patients with high SUZ12 expression had poorer prognoses. In LM3 and Huh7 liver cancer cell lines, stable knockdown of SUZ12 reduced cell proliferation ability. In the de novo MYC/Trp53^-/- mouse liver cancer model, tumor nodule number and size, and tumor burden in liver tissue were reduced after endogenous knockout of Suz12. TCGA analysis showed that high SUZ12 expression in HCC was enriched in multiple tumor proliferation- and metabolism-related pathways. The expression of SUZ12 was positively correlated with CSC markers and key genes in glycolysis pathway. The mRNA levels of CSC markers and key genes in glycolysis pathway were decreased in liver cancer cell lines with stable SUZ12 knockdown and Suz12 knockout mouse HCC tissues. Conclusion ·The expression of SUZ12 is significantly increased in HCC patients and is associated with poor prognosis. Stable knockdown of SUZ12 weakens the proliferative ability of liver cancer cells. Knockout of Suz12 in mice in vivo can suppress the occurrence and development of HCC. The high expression of SUZ12 maintains the CSC pool, induces metabolic reprogramming, and promotes the occurrence and progression of HCC. SUZ12 can serve as a potential biomarker for poor prognosis and a novel target for potential therapeutic intervention in HCC.

Key words: suppressor of zeste 12 (SUZ12), hepatocellular carcinoma (HCC), hydrodynamic tail vein injection, therapeutic target

CLC Number:

R735.7

LI Qianyu, QIAN Yifei, LI Songling, ZHU Zijun, QIN Wenli, LIU Yanfeng, QIU Bijun. Function and mechanism of suppressor of zeste 12 in hepatocellular carcinoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(9): 1138-1148.

Figures/Tables 6

TrendMD

References 37

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Gene	Forward (5′→3′)	Reverse (5′→3′)
SUZ12	AGGCTGACCACGAGCTTTTC	GGTGCTATGAGATTCCGAGTTC
CD13	GACGCTGAGACCGTACCTC	TCAGTCTTGTCAATGTCGGGG
EpCAM	AATCGTCAATGCCAGTGTACTT	TCTCATCGCAGTCAGGATCATAA
CD24	CTCCTACCCACGCAGATTTATTC	AGAGTGAGACCACGAAGAGAC
PKM2	ATAACGCCTACATGGAAAAGTGT	TAAGCCCATCATCCACGTAGA
HK2	TTGACCAGGAGATTGACATGGG	CAACCGCATCAGGACCTCA
PGK1	TGGACGTTAAAGGGAAGCGG	GCTCATAAGGACTACCGACTTGG
ACTB	CATGTACGTTGCTATCCAGGC	CTCCTTAATGTCACGCACGAT
Cd13	ATGGAAGGAGGCGTCAAGAAA	CGGATAGGGCTTGGACTCTTT
Epcam	GCGGCTCAGAGAGACTGTG	CCAAGCATTTAGACGCCAGTTT
Cd24	GTTGCACCGTTTCCCGGTAA	CCCCTCTGGTGGTAGCGTTA
Cd34	AAGGCTGGGTGAAGACCCTTA	TGAATGGCCGTTTCTGGAAGT
Cd44	TCGATTTGAATGTAACCTGCCG	CAGTCCGGGAGATACTGTAGC
Pkm2	GCCGCCTGGACATTGACTC	CCATGAGAGAAATTCAGCCGAG
Hk2	TGATCGCCTGCTTATTCACGG	AACCGCCTAGAAATCTCCAGA
Pgk1	ATGTCGCTTTCCAACAAGCTG	GCTCCATTGTCCAAGCAGAAT
Actb	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT

Gene	Forward (5′→3′)	Reverse (5′→3′)
SUZ12	AGGCTGACCACGAGCTTTTC	GGTGCTATGAGATTCCGAGTTC
CD13	GACGCTGAGACCGTACCTC	TCAGTCTTGTCAATGTCGGGG
EpCAM	AATCGTCAATGCCAGTGTACTT	TCTCATCGCAGTCAGGATCATAA
CD24	CTCCTACCCACGCAGATTTATTC	AGAGTGAGACCACGAAGAGAC
PKM2	ATAACGCCTACATGGAAAAGTGT	TAAGCCCATCATCCACGTAGA
HK2	TTGACCAGGAGATTGACATGGG	CAACCGCATCAGGACCTCA
PGK1	TGGACGTTAAAGGGAAGCGG	GCTCATAAGGACTACCGACTTGG
ACTB	CATGTACGTTGCTATCCAGGC	CTCCTTAATGTCACGCACGAT
Cd13	ATGGAAGGAGGCGTCAAGAAA	CGGATAGGGCTTGGACTCTTT
Epcam	GCGGCTCAGAGAGACTGTG	CCAAGCATTTAGACGCCAGTTT
Cd24	GTTGCACCGTTTCCCGGTAA	CCCCTCTGGTGGTAGCGTTA
Cd34	AAGGCTGGGTGAAGACCCTTA	TGAATGGCCGTTTCTGGAAGT
Cd44	TCGATTTGAATGTAACCTGCCG	CAGTCCGGGAGATACTGTAGC
Pkm2	GCCGCCTGGACATTGACTC	CCATGAGAGAAATTCAGCCGAG
Hk2	TGATCGCCTGCTTATTCACGG	AACCGCCTAGAAATCTCCAGA
Pgk1	ATGTCGCTTTCCAACAAGCTG	GCTCCATTGTCCAAGCAGAAT
Actb	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT