The Research Of REGγ In Expression And Function Of Osteosarcoma

Research background and objectiveOsteosarcoma(OS)is a malignant tumor that originates from mesenchymal tissue.It is the most common primary malignant bone tumor,which occurs worldwide every year.The rate is 1-3/1 million,and men are higher than women.It has a high degree of malignancy and a very poor prognosis.There is currently no effective cure.Osteosarcoma occurs in fast-growing bone tissue,often occurring in the long bones of the extremities,accounting for about 80%,most commonly in the long bones around the knee joint.Osteosarcoma can occur in all ages,especially in adolescents,accounting for about 5% of adolescent tumors,rapid disease progression,lung metastasis in a short period of time,poor treatment and low 5-year survival rate.Not only cause great pain to patients and families of osteosarcoma,but also affect the allocation of medical resources in China.The proteasome activator REGγ is a member of the proteasome activator REG(aka 11S)family and degrades proteins in a non-ubiquitinated and non-ATP-dependent manner.In recent years,more and more studies have shown that REGγ is abnormally expressed in a variety of tumors and is closely related to the occurrence and development of tumors.REGγ participates in the development of tumors mainly by degrading a variety of target proteins and regulating related signaling pathways.REGγ has been shown to be closely related to the malignant oncology behavior of proliferation and migration of various tumors,but no related studies of osteosarcoma have been reported.This research topic is to study the expression and function of REGγ in osteosarcoma.Research on REGγ and tumor has become a hot spot in research at home and abroad.By collecting clinical osteosarcoma patients,the expression level and prognosis of REGγ in osteosarcoma were detected,and the role and relationship of REGγ in the development of osteosarcoma were discussed.Furthermore,the effects of REGγ and osteosarcoma cell proliferation and migration on tumor biological behavior were further explored at the cellular level.To provide a theoretical basis for further exploration of the pathogenesis of osteosarcoma and new drug targets.The research methods1.To collect the tumor specimens of patients with clinical osteosarcoma,and to evaluate the expression of REGγ in osteosarcoma by immunohistochemical staining,and to analyze the prognosis correlation with clinical follow-up data;2.Interfering with the expression of REGγ in osteosarcoma cell lines,establishing a stable transfected cell line of REGγ,and observing the changes of malignant biological behavior such as tumor cell proliferation and migration;3.The lung metastasis model of osteosarcoma in nude mice was established by injection of osteosarcoma cells into the tail vein.The lung metastasis of the two groups was compared.Research results:1.Immunohistochemistry demonstrated that the REGγexpression in osteosarcoma tissue was abruptly higher than normal tissue.The expression level of REGγ in normal tissues was relatively low.The high expression of REGγ in osteosarcoma was significantly correlated with the poor prognosis of patients.Patients with high expression of REGγ in osteosarcoma have a worse prognosis than patients with low REGγ expression;2.In the osteosarcoma stable cell line,the biological behavior of tumor cells showed a significant decrease in proliferative capacity,invasive ability and migration ability after REGγ knockdown;3.Lung sarcoma lung metastasis model was established by injection of osteosarcoma cells into the tail vein.It was observed that mice with REGγ knockdown osteosarcoma cells in the tail vein had fewer lung tumor metastases and smaller volume.The research conclusion1.The REGγexpression in osteosarcoma tissue is abruptly higher than normal tissue which indicates that REGy may be firmly related with tumor progression.The expression of REGγ is significantly correlated with the median survival time of osteosarcoma patients.Patients with higher expression levels have a worse prognosis;(P<0.05)2.The results of REGγ-stable osteosarcoma cell function showed that the proliferative capacity,migration ability and invasion ability of osteosarcoma cells after proteasome REGγ knockdown were significantly decreased.3.The results of animal tumor test showed that compared with the non-knockout,the lung metastasis of the nude mice with REGγknockdown osteosarcoma cells was significantly less and smaller.REGγ is closely related to the occurrence of osteosarcoma,malignant oncology and prognosis.This provides an important research direction for improving the research on osteosarcoma related mechanisms and targeted drug development and even cure rate.