Uncovering the Multifaceted Role of the Kinetochore Scaffold 1 (KNL1) in Hepatocellular Carcinoma: Integrative Bioinformatics Analysis and CRISPR-Cas9 Experimental Study

KNL1 is markedly overexpressed in hepatocellular carcinoma, especially with TP53 mutations, and a KNL1-G2M network score predicts poorer overall survival and higher chromosomal instability.

• Why it matters: The role of this mitotic checkpoint scaffold in HCC is unclear, despite links to heterogeneity, chromosomal instability, and limited treatment options.
• What they did: The study integrated bulk and single-cell transcriptomics with WGCNA/hallmark enrichment to define a KNL1-associated G2M checkpoint network, then used CRISPR-Cas9 to downregulate KNL1 in HepG2 cells.
• The result: High KNL1-G2M scores associate with increased proliferation, chromosomal instability, T-regulatory cells and M0 macrophages, and higher TIDE/exclusion scores, while KNL1 knockdown modestly arrests G2/M, suppresses proliferation, reduces survivin and Bcl2, and shows early apoptosis ultrastructural changes.

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