Reptin regulates tumor cell growth and cisplatin resistance in osteosarcoma

Purpose: Osteosarcoma is the most common primary bone tumor with poor prognosis, characterized by high recurrence and metastasis. Recent studies show that Reptin is overexpressed in several malignant tumors and is required for tumorigenesis. Reptin is thought to be involved in chromatin remodeling and DNA damage repair. However, the biological function and the molecular mechanism of Reptin in osteosarcoma are still not fully understood. Methods The expression of Reptin was detected in 59 osteosarcoma and 35 non-neoplastic bone specimens by immunohistochemistry. Kaplan -Meier curves was used to evaluate the prognostic significance of Reptin. Then we knockdown the expression of Reptin in Saos-2 and U2OS cells. MTT, Edu assay, flow cytometry, wound-healing and transwell assays were performed to examine the influences of Reptin expression on cell proliferation, cell cycle, migration and invasion. We further conducted co-immunoprecipitation experiments to explore the relationship between Reptin and DNA-PKcs. Finally, we determined the role of Reptin on DNA damage repair and chemosensitivity of cisplatin. Results We verified that high expression of Reptin was closely associated with tumor differentiation, Enneking stage and metastasis. Patients with Reptin-positive staining exhibited a significantly decreased overall survival. Additionally, we found that Reptin deleption inhibited the proliferation, invasion of osteosarcoma cells and caused G1 arrest. Furthermore, we discovered that Reptin participate in DNA damage repair through interaction with DNA-PKcs, inhibition of Reptin expression in osteosarcoma cells enhances cisplatin sensitivity by aggravating DNA damage. Conclusions In summary, we revealed that Reptin plays a crucial role in tumor growth and may serve as an attractive therapeutic target for osteosarcoma.