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Article Abstract
Introduction: This study aims to explore the potential of LMNB1 and LMNB2 as prognostic risk factors in hepatocellular carcinoma (HCC) and investigate small-molecule drugs targeting both for therapeutic application.
Methods: LMNB1 and LMNB2 expression in HCC was assessed using TCGA data and validated in clinical specimens. Kaplan-Meier and Cox models evaluated prognostic relevance. Drug sensitivity screening using CTRP and GDSC databases highlighted GSK461364 (a selective PLK1 inhibitor), whose effects were validated in Hep3B and SK-HEP-1.
Results: LMNB1 and LMNB2 were aberrantly up-regulated in HCC tissues and contributed to the poor prognosis of HCC patients. Co-expression modules and enriched pathways of LMNB1 and LMNB2 were linked to nuclear architecture and cell senescence, indicating their roles in genomic stability and cell cycle progression. GSK461364 was validated to inhibit the cell viability of HCC cells. It suppressed the expression of LMNB1 and LMNB2 but not PLK1, suggesting its anti-HCC effect depends on inhibition of LMNB1/2 rather than PLK1.
Discussion: Our findings suggest that LMNB1 and LMNB2 could serve as prognostic biomarkers. GSK461364 likely exerts anti-HCC effects through suppression of LMNB1 and LMNB2 expression. Further in vivo validation and molecular mechanism studies are needed to establish its clinical utility.
Conclusion: LMNB1 and LMNB2 are prognostic factors for HCC. GSK461364 is a novel therapeutic candidate for HCC, with anti-HCC effects associated with LMNB1/2 suppression.
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| http://dx.doi.org/10.2174/0115748928375684250716120144 | DOI Listing |
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