Study On The Expression And Function Of REGγ In Ewing’s Sarcoma

[background] Ewing’s sarcoma(ES)is the second most common bone tumor in children and adolescents,and its annual incidence is 2.93/1 000000.ES is an invasive bone and soft tissue sarcoma,often found in bones,especially in the lower extremities(41%),pelvis(26%),chest wall(16%),vertebrae(6%)and skull(2%).The clinical symptoms of ES is not obvious and difficult to detect.About 1/4 of ES patients have metastasize at diagnosis.The lung is the most common metastatic site(50%),followed by bone(25%)and bone marrow(20%).ES is very sensitive to radiotherapy.Small doses of radiation can rapidly reduce the tumor and the local pain in patients is significantly reduced.It is worth noting that radiotherapy will easily cause spinal nerve injury to the vertebral body,and even cause patient paralysis because of the irreversible damage of the nerve function.In addition,early ES is prone to distal metastasis,and the long term effect of simple radiotherapy is poor.However,the specific pathogenesis of ES is not clear.Proteasome system is one of the most important regulatory systems in vivo.Protein degradation system can regulate cell processes,such as cell cycle,transcription,cell signal transduction,cell death and immune response.REG gamma,also known as PA28 gamma,11 S gamma or Proteasome activator complex subunit 3,PSME3,is a member of the 20 S proteasome activating factor family,mainly located in the nucleus.REG gamma as an important proteasome activator,form seven homologous polymer and participates in the regulation of many diseases related pathways.REG gamma promotes the degradation of target proteins in non-ubiquitin and non-ATP-dependent manner,such as SRC-3,P21,P53,P16,CK-1Delta,Sir T1 and so on.The study confirmed that REG gamma is highly expressed in many cancer tissues and promote their development,such as colon cancer,lung cancer,gastric carcinoma,chordoma and so on.However,there is no report on the role of REG gamma in ES.Therefore,the study of REG gamma in ES provides a theoretical basis for the exploration of pathogenesis and the improvement of cure rate.[Objective] To explore the role and relationship of REG gamma in the development of Ewing’s sarcoma by detecting the expression level and prognosis of REG gamma in Ewing’s sarcoma.This project provides more ideas for the exploration of pathogenesis and the improvement of cure rate.[Methods] 1.Immunohistochemical staining was used to evaluate the expression of REG gamma in ES tissues,and clinical follow-up data were collected to analyze theircorrelation;2.To establish the primary ES cell line from resection of ES organization;3.The expression of REG gamma was downregulated in the primary ES cells,the expression level and biological behavior of the tumor cells were detected;4.The expression of REG gamma was overexpressed in the primary ES cells,the expression level and biological behavior of the tumor cells were detected.[results] 1.REGγ expression in Ewing’s sarcoma was significantly higher than that in the normal tissue around the tumor,REG expression in normal tissue adjacent is at a relatively low level;2.The high expression of REG gamma in ES tissues was associated with poor prognosis;3.Knockdown of REG gamma induces more apoptosis and less proliferation,invasion and migration ability in Ewing’s sarcoma cells;4.Overexpression of REG gamma induces less apoptosis and more proliferation,invasion and migration ability in Ewing’s sarcoma cells.[conclusions] 1.REG expression was significantly higher than that in tumor adjacent normal tissues in Ewing’s sarcoma,suggesting that REGy may promote tumor cell growth;2.The expression of REGy was negatively correlated with no survival time of Ewing sarcoma patients;3.Knockdown of REG gamma induces more apoptosis and less proliferation,invasion and migration ability in Ewing’s sarcoma cells.The proliferation,migration and invasiveness of Ewing’s sarcoma cells were obviously enhanced after REG gamma overexpression.REG gamma is closely related to the recurrence and prognosis of Ewing’s sarcoma.It will provide a very important way to improve the cure rate of Ewing sarcoma.