HLTF Promotes the Proliferation of Osteosarcoma Cells and Cisplatin Resistance.

Abstract

Background: Osteosarcoma, the most common primary malignant tumor of bone tissue, is characterized by aggressive biological behavior and poor clinical outcomes. The Helicase-Like Transcription Factor (HLTF), a key regulator of DNA damage response and chromatin remodeling processes, has been increasingly recognized for its crucial role in the pathogenesis and progression of various malignancies.

Objective: This study aimed to elucidate the regulatory role of HLTF in modulating critical cellular processes, including proliferation, migration, and apoptosis in osteosarcoma cells, while concurrently investigating its potential as a molecular determinant of cisplatin chemoresistance.

Methods: The CCK-8 and colony formation assays were carried out to systematically evaluate the impact of HLTF on the proliferative capabilities of osteosarcoma cells. Additionally, the transwell and cell scratch assays were performed to determine the effect of HLTF on the migratory potential of osteosarcoma cells. Furthermore, the CCK8 assay and the subcutaneous tumorigenesis experiment were conducted in nude mice to determine the effect of HLTF on the sensitivity of osteosarcoma cells to cisplatin.

Results: Our findings revealed that silencing HLTF expression in osteosarcoma cells led to a marked suppression of both cell proliferation and invasive potential. In contrast, the overexpression of HLTF was found to augment the proliferative and migratory abilities of these cells. Remarkably, downregulating HLTF in osteosarcoma cells heightened cell sensitivity to cisplatin, which was further validated by in vivo experiments.

Conclusion: Collectively, our findings strongly indicate that HLTF acts as an oncogene, actively driving the proliferation of osteosarcoma cells and conferring resistance to cisplatin.