| Background and Objective:Osteosarcoma is the most common primary malignant bone tumor,and its development is determined by multiple factors,including the most important genetic aberrations and the microenvironment conducive to tumor growth.The current treatment mode of osteosarcoma includes surgery,chemotherapy,radiotherapy,multi-target TKI and immunotherapy,etc.,but there is no significant improvement in the prognosis of patients with multiple metastases and recurrent osteosarcoma.Therefore,the clinical practice of osteosarcoma needs new therapies and treatment strategies.The mHA-I is a novel tubulin inhibitor of colchicine site designed and developed by our group.The results of previous studies showed that mHA-I has potent anti-tumor effect on osteosarcoma.The results of transcriptome analysis of osteosarcoma cells treated with mHA-I and control group showed that the expression level of SPRED2 may play a tumor suppressor role as a potential target for drug action.SPRED2 is an important member of the SPREDs protein family,which is closely related to the development of various malignancies,but the specific role that SPRED2 plays in osteosarcoma is not clear.Therefore,we plan to further explore the functional characteristics of SPRED2,expression in osteosarcoma,the impact on the biological characteristics of osteosarcoma cells,prognosis with survival and other clinical features,and initially explore the related mechanism,in order to explore the function of SPRED2 molecules,and finally provide possible and effective new strategies for osteosarcoma treatment.Methods:1.apply TIMER database and Ualcan database to study the expression of SPRED2 in various tumors and its functional characteristics;apply GEO database to clarify the expression of SPRED2 in osteosarcoma;2.explore the effect of SPRED2 on osteosarcoma by CCK-8,apoptosis,cell scratching,Transwell and other in vitro experiments and nude mice subcutaneous tumorigenesis experiment;3.Immunohistochemistry was used to verify the expression of SPRED2 in clinical osteosarcoma specimens and further analyze the relationship between SPRED2 and clinicopathological parameters and prognosis of osteosarcoma patients;ESTIMATE and TIMER algorithms were applied to evaluate the relationship between SPRED2 and the immune microenvironment of osteosarcoma;gene set enrichment analysis was performed to predict the possible role of SPRED2 in osteosarcoma The possible signaling pathways and biological functions of SPRED2 in osteosarcoma were predicted by gene set enrichment analysis.Results:SPRED2 is aberrantly expressed in a variety of tumors and affects tumor prognosis;SPRED2-related proteins,biological functions and related pathways are closely related to tumor development;SPRED2 is highly expressed in osteosarcoma.2.Knockdown of SPRED2 expression significantly inhibited the proliferation,invasion,migration and subcutaneous tumorigenic ability of osteosarcoma cells in nude mice.3.The results of enrichment analysis showed that tumor-associated signaling pathways and biological functions that promote tumor growth were enriched in the SPRED2 high expression group;there was more abundant immune cell infiltration in the SPRED2 high expression group than in the low expression group.Conclusion:SPRED2 is involved in a variety of tumor-related signaling pathways and has the biological function of promoting tumor growth,and its abnormal expression may be a key regulatory point in tumor development;SPRED2 is highly expressed in osteosarcoma,and inhibition of SPRED2 expression can significantly inhibit the malignant biological behavior of osteosarcoma cells,so SPRED2 may act as a potential pro-oncogene in osteosarcoma to mediate the progression of osteosarcoma;the results of survival analysis showed that patients in the group with high SPRED2 expression had a better prognosis than those in the group with low expression,which may be associated with a more abundant immune cell infiltration. |
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