The relationship between PM20D1 gene and hypoxia and prognosis in diffuse large B-cell lymphoma was analyzed by integrating multiple databases
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Abstract:
Objective::To investigate the expression of peptidase M20 domain 1 (PM20D1) in human diffuse large B-cell lymphoma (DLBCL) cells and its relationship with hypoxia and prognosis. Methods: The effects of PM20D1 expression on proliferation,migration and apoptosis of DLBCL cells and its relationship with patients' prognosis were analyzed through GDC, TCGA and GTEx public databases. The enrichment analysis of patients in different groups and the correlation analysis between PM20D1 and CD274 were used to validate whether PM20D1 was the hypoxia-related gene of DLBCL. ChEA, ENCODE and hTFtarget databases were used to analyze the transcription factors (TFs) and miRNAs that upstream regulate PM20D1 expression and the relationship between differential expression of PM20D1 and chemotherapeutic drug sensitivity. The expression level of PM20D1 in normal lymphocytes and DLBCL cells was detected by WB method, the target gene was reduced by the siRNA sequence of PM20D1, and the knockdown efficiency of PM20D1 in SUDHL2 and SUDHL10 cells was verified by qPCR and WB methods.The effect of PM20D1 on cell proliferation and migration ability after knockdown was detected by CCK-8 method and Transwell assays, respectively, and the apoptosis level was detected by flow cytometry. Results: PM20D1 was highly expressed in DLBCL tissues and was correlated with a poor prognosis (P<0.05 or P<0.01).Enrichment analysis showed that the PM20D1 high expression group and high ssGSEA score group were mainly involved in cellular electrocoupling communication, triglyceride metabolism process regulation and cytoplasmic translation initiation complex process, and PM20D1 expression was positively correlated with CD274 expression at immune checkpoint (P<0.01, r=0.757). After knocking down PM20D1 in SUDHL2 and SUDHL10 cells, the proliferation and migration of cells decreased significantly (all P<0.05), and apoptosis increased significantly (P<0.05). Conclusion: PM20D1 gene was highly expressed in DLBCL tissues and cells, and in closely related to patient prognosis. PM20D1 may promote the occurrence and development of DLBCL by promoting the proliferation, migration and inhibiting the apoptosis of DLBCL cells.