Objective Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression. Methods In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis. Results ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways. Conclusion Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.

Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs for treatment of osteosarcoma, but multidrug resistance is a growing problem. Therefore, understanding the molecular mechanisms of chemotherapy resistance in osteosarcoma cells is crucial for developing new therapeutic approaches and ultimately improving the prognosis of osteosarcoma patients. To identify genes associated with cisplatin resistance in osteosarcoma, we screened a large‐scale mutant library generated by transfecting human osteosarcoma cells with a piggyBac (PB) transposon‐based gene activation vector. Several candidate genes were identified by using Splinkerette‐PCR paired with Next Generation Sequencing. We created a disease‐free survival predictor model, which includes ZNF720 , REEP3 , CNNM2 , and CGREF1 , using TARGET (Therapeutically Applicable Research to Generate Effective Treatments) datasets. Additionally, the results of our enrichment analysis between the Four_genes_high group and Low_group suggested that these four genes may participate in cisplatin resistance in osteosarcoma through cross talk between various signaling pathways, especially the signaling pathway related to bone formation. These data may help guide future studies into chemotherapy for osteosarcoma.

It has been reported that neurotrophic factor (NF) promotes bone marrow mesenchymal stem cells (MSCs) migration to repair fractures. However, whether and how lncRNA PVT1 regulates differentiation induced by neurotrophic factors to promote MSC migration to repair fractures has not been explored. To explore the molecular mechanism of neurotrophic factor activating lncRNA PVT1 to promote MSC migration and repair fractures. Differential expression of neurotrophic factors stimulated by MSCs was analyzed based on microarray lncRNA and lncRNAs was further verified by qRT-PCR. The conditions of promoting MSC migration and osteogenic differentiation were identified by trans-fection of lncRNA PVT1 overexpressed plasmids and inhibitor and the targets of its regulation were confirmed by target gene prediction tools. In this study lncRNA array and qRT-PCR showed that lncRNA PVT1 was significantly down-regulated during neurotrophic factor-induced MSCs differentiation. Transfection of lncRNA PVT1 overexpression plasmid significantly inhibited the expression of osteogenic markers alkaline phosphatase (ALP) and osteopontin (OPN) in MSCs, while transfection of lncRNA PVT1 inhibitor promoted the expression of alkaline phosphatase (ALP) and osteopontin (OPN). lncRNA PVT1 is a negative regulator of MSCs differentiation induced by neurotrophic factors. The distal deletion homologous box 5(DLX5) was identified as the target of lncRNA PVT1 and the relationship between lncRNA PVT1 inhibiting the expression of DLX5 and the osteogenic differentiation of MSCs was verified in MSCs. lncRNA PVT1 negatively regulates the migration and differentiation of MSCs induced by neurotrophic factors by targeting DLX5, providing the foundation for bone repair.