March 3, 2026SHILAP Revista de lepidopterología0 citationsOpen Access

Multi-omics comprehensive analysis identified KIF22 and KRAS as highly synthetic lethal pairs for triple-negative breast cancer

SMShichen MiaoNantong University XWXiao WangNantong University QGQiming GuNantong University

Key Points

KIF22 and KRAS are validated as a synthetic lethal gene pair in triple-negative breast cancer.
In KRAS-mutated cells, knockdown of KIF22 significantly inhibits cell proliferation, highlighting therapeutic potential.
Assessment using bioinformatics and experimental validation suggests a promising path for drug development.
The findings suggest a strong potential for KIF22 as a therapeutic target due to its interaction with KRAS mutations.

Abstract

In conclusion, this study systematically characterized the heterogeneity of TNBC and explored the association between SL activity and disease progression through a comprehensive analysis of the interactions between SL pairs and malignant TNBC cells. Our findings contribute to a deeper understanding of the molecular mechanisms underlying TNBC initiation and development. Based on bioinformatics analyses, we experimentally validated KIF22 and KRAS as a synthetic lethal gene pair in TNBC. Functional experiments demonstrated that the knockdown of KIF22 in KRAS-mutated TNBC cells or the knockdown of KRAS in TNBC cells with low expression of KIF22 gene significantly inhibited cell proliferation. Given the high prevalence of KRAS mutations in TNBC, KIF22 represents a promising therapeutic target for synthetic lethal intervention. Furthermore, in vivo xenograft models confirmed that concurrent knockdown of murine KIF22 and KRAS effectively inhibited tumor progression. Collectively, these results establish KIF22 and KRAS as a TNBC-specific synthetic lethal pair with strong potential for guiding future SL-based drug discovery efforts.

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