Integrated multi-omics analysis revealed that SMARCAL1 serves as an immune related prognostic marker and promotes liver cancer growth via the Hippo/YAP signaling axis

Objective: To illustrate the potential role of SMARCAL1 on malignancy, immune regulation and related pathway in liver Cancer.

Methods: In our study, we examined the expression patterns, clinical features and survival analysis from TCGA and GEO datasets. Immunedeconv package was employed for evaluating the association between the immune infiltration components and SMARCAL1 expression. Knockdown experiment was performed to examine the impacts of SMARCAL1 on cell viability, Apoptosis, and classical Hippo-YAP pathway. Meanwhile, the association between SMARCAL1 expression and drug sensitivity was constructed through CTRP, PRISM and GDSC databases. Finally, we also discovered novel inhibitors of SMARCAL1 activity against liver Cancer and YAP activity through virtual screening and western blot assay.

Results: SMARCAL1 exhibited increased expression in LIHC and was linked to unfavorable outcomes for patients. SMARCAL1 expression was associated with specific clinical features, drug sensitivity, and immune microenvironment characteristics. Additionally, SMARCAL1 was closely related to the activity of Hippo-YAP pathway. Finally, deferoxamine mesylate and its parent compound deferoxamine were identified as candidate inhibitors of SMARCAL1 activity, showing significant ability to inhibit proliferation and the downstream protein YAP1.

Conclusion: Targeting SMARCAL1 could be a promising strategy for liver Cancer treatment.