The Role And Mechanism Of TMPRSS2-ERG Fusion Gene Regulating INSM1 In The Occurrence And Development Of Prostate Cancer

Prostate cancer is the highest incidence of male malignant tumor and has become one of the common causes of death in men in different countries and regions.Although the incidence of prostate cancer in China is lower than the global level,with the improvement of social development and detection level,the incidence of prostate cancer has been increasing rapidly in recent years,and the number of deaths caused by prostate cancer is also increasing.At the same time,due to the heterogeneity and complexity of prostate cancer,the response of patients to treatment is different,and the prognosis is significantly different.Therefore,it is necessary to further study the pathogenesis of prostate cancer.Insulinoma-associated antigen 1(IA-1/INSM1)is a transcription inhibitor.Currently,INSM1 is mainly used as a diagnostic marker for prostate cancer,especially for specific pathological types of prostate cancer,such as small cell cancer and neuroendocrine prostate cancer.However,the mechanism of INSM1 in the occurrence and progression of prostate cancer is still insufficient to be explored.In this study,we found that the expression level of INSM1 in prostate cancer was abnormally elevated through public database and prostate cancer specimen analysis.In addition,its expression level is positively correlated with the clinical grade of prostate cancer and negatively correlated with the survival prognosis of prostate cancer,that is,patients with high INSM1 expression level have higher clinical grade and poorer survival prognosis.In cell functional experiments,it was found that INSM1 can promote the proliferation and invasion ability of tumor cells.In the mechanism study,we found that the expression level of INSM1 in ERG protein-positive VCa P cells was the highest,and we also found a positive correlation between ERG and INSM1 gene expression levels through public database and prostate cancer specimen analysis.ERG gene is a oncogenic gene,which can be fused with TMPRSS2 gene in some prostate cancer patients,resulting in abnormal high expression and oncogenic effect.Further studies showed that ERG protein in prostate cancer could promote the transcription of INSM1 gene by binding to the INSM1 gene promoter region.The increased expression of INSM1 can further bind to the transcriptional initiation region of tumor suppressor gene PTEN and inhibit the transcriptional expression of PTEN gene.Ultimately,decreased PTEN gene expression leads to abnormal activation of the PI3K/AKT/m TOR pathway in cells,thereby promoting tumor progression.This study found that INSM1 is highly expressed in prostate cancer and plays a carcinogenic role,EGR protein regulates INSM1 expression in prostate cancer.However,abnormally high expression of INSM1 can further down-regulate the expression of PTEN gene,and ultimately lead to abnormal activation of PI3K/AKT/m TOR pathway,thus promoting the development of prostate cancer.This study suggests that INSM1 may be a novel therapeutic target for prostate cancer,especially in patients with TMPRSS2-ERG fusion mutations.