Malic enzyme 2 promotes liver cancer progression by regulating SHCBP1

doi:10.16352/j.issn.1001-6325.2025.06.0741

Abstract

Abstract: Objective To identify genes regulated by ME2 and to explore their roles as well as underlying mechanisms in liver cancer progression. Methods RNA-seq data of siME2-transfected cells were subjected to differential expression analysis, clustering, GO and KEGG enrichment analyses. The mRNA level of the potential target gene SHCBP1 was measured by quantitative real-time PCR (qPCR) following ME2 knockdown or overexpression in HepG2 cells. The effect of ME2 and SHCBP1 on the downstream pathway was examined by Western blot. Cell proliferation, wound healing, and colony formation assays were conducted to evaluate SHCBP1's role in liver cancer cell proliferation and migration. Survival analysis of the TCGA-LIHC cohort was performed to determine the prognostic value of SHCBP1 in liver cancer patients. Results Differentially expressed genes in siME2-transfected cells were significantly enriched in biological processes including the PI3K-Akt signaling pathway, cell cycle, and serine phosphorylation. In HepG2 cells, ME2 knockdown led to a reduction in SHCBP1 mRNA level, whereas ME2 over-expression resulted in enhanced SHCBP1 mRNA level, demonstrating a positive correlation between ME2 and SHCBP1 expression. Western blot analysis revealed that ME2 enhanced PI3K-Akt signaling pathway activation through SHCBP1. qPCR results confirmed that SHCBP1 was significantly over-expressed in liver cancer cells and promoted both proliferation and migration, contributing to poor prognosis in liver cancer patients. Conclusions ME2 promotes liver cancer progression by regulating SHCBP1 to activate the PI3K-Akt signaling pathway, presenting a novel therapeutic target for liver cancer treatment.

Key words: malic enzyme 2 (ME2), PI3K-Akt signaling pathway, SHCBP1, liver cancer

CLC Number:

R735.7

QIU Yuchong, DU Wenjing. Malic enzyme 2 promotes liver cancer progression by regulating SHCBP1[J]. Basic & Clinical Medicine, 2025, 45(6): 741-747.

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