ABLIM1 promotes the proliferation, migration and invasion of osteosarcoma through DCC mediated activation of PI3K/AKT signaling pathway

Background: Actin-binding LIM protein 1 (ABLIM1) is a member of the LIM domain protein family and has been identified as a novel E3 ubiquitin Ligase. However, its precise biological function remains incompletely characterized. This study aimed to investigate the role of ABLIM1 in modulating the biological behavior of osteosarcoma cells and elucidate the underlying molecular mechanisms.

Methods: Through integrated bioinformatic analyses and experimental validation, we characterized ABLIM1 dysregulation in osteosarcoma and evaluated its prognostic significance. To determine ABLIM1's impact on osteosarcoma cell proliferation, migration, and invasion, we conducted comprehensive in vitro functional assays including CCK-8, EdU incorporation, wound healing, and Transwell invasion analyses. Subsequent investigation of ABLIM1-associated downstream pathways employed Western blotting and metabolic profiling, followed by rigorous validation experiments. Finally, we established a subcutaneous xenograft tumor model in nude mice to assess ABLIM1's in vivo functions.

Results: Silencing ABLIM1 significantly inhibited the proliferation, migration and invasion of osteosarcoma cells. On the contrary, overexpression of ABLIM1 resulted in the converse phenotype. In animal models, we injected silenced ABLIM1 143B osteosarcoma cells subcutaneously. The results showed that inhibiting the expression of ABLIM1 impaired the growth of osteosarcoma.

Conclusion: Our research results indicate that ABLIM1 may be an independent prognostic factor for individuals diagnosed with osteosarcoma. By regulating the DCC/PI3K/Akt/mTOR axis, ABLIM1 promotes the growth, migration and invasion of osteosarcoma cells. Therefore, targeting ABLIM1 may serve as an effective therapeutic target for the treatment of osteosarcoma.

ABLIM1; DCC/PI3K/AKT/mTOR axis; E3 ubiquitin ligase; Osteosarcoma; Therapeutic.