Evidence of Omics, Immune Infiltration, and Pharmacogenomic for SENP1 in the Pan-Cancer Cohort

Abstract

Sentrin specific-protease 1 (SENP1) is a protein involved in deSUMOylation that is almost overexpressed in cancer. SENP1 has a determinative role in the activation of transcription programs in the innate immune responses and the development B of and C lymphocytes. We found, SENP1 possibly plays a critical role in immune infiltration and acts as an expression marker in PAAD, ESCA, and THYM. CD4+ T cells, CD8+ T cells, and macrophages were more key-related immune cells, indicating that SENP1 might be introduced as a potential target for cancer immunotherapy. We further showed that dysregulation of SENP1 is powerfully associated with decreased patient survival and clinical stage. Total SENP1 protein also increases in cancer. SENP1 is also controlled by transcription factors (TFs) CREB1, KDM5A, REST, and YY1 that regulates apoptosis, cell cycle, cell proliferation, invasion, tumorigenesis, and metastasis. These TFs were in a positive correlation with SENP1. MiR-138–5p, miR-129-1-3p, and miR-129-2-3p also inhibit tumorigenesis through targeting of SENP1. The SENP1 expression level positively correlated with the expression levels of UBN1, SP3, SAP130, NUP98, NUP153 in 32 tumor types. SENP1 and correlated and binding genes: SAP130, NUP98, and NUP153 activated cell cycle. Consistent with this finding, drug analysis was indicated SENP1 is sensitive to cell cycle, apoptosis, and RTK signaling regulators. In the end, SENP1 and its expression-correlated and functional binding genes were enriched in cell cycle, apoptosis, cellular response to DNA damage stimulus. We found that the cell cycle is the main way for tumorigenesis by SENP1. SENP1 attenuates the effect of inhibitory drugs on the cell cycle. We also introduced effective FDA-Approved drugs that can inhibit SENP1. Therefore in the treatments in which these drugs are used, SENP1 inhibition is a suitable approach. This study supplies a wide analysis of the SENP1 across The Cancer Genome Atlas (CGA) cancer types. These results suggest the potential roles of SENP1 as a biomarker for cancer. Since these drugs and the drugs that cause to resistance are applied to cancer treatment, then these two class drugs can use to inhibition of SENP1.

New Insights Into PTBP3 in Human Cancers: Immune Cell Infiltration, TMB, MSI, PDCD1 and m6A Markers

“…However, the oncogenic role of PTBP3 in various human tumours remains unclear. A pan-cancer analysis can identify the difference between normal and tumour tissues, providing a comprehensive understanding of the molecular mechanisms of tumorigenesis and progression ( Chakravorty et al, 2019 ; Chai et al, 2020 ; Chen et al, 2021 ; Fiala et al, 2021 ; Taghvaei et al, 2021 ). Thus, we performed a pan-cancer analysis of the gene expression profile, survival status, genetic alteration, protein phosphorylation, immune infiltration, N6-methyladenosine, and relevant cellular pathways of PTBP3 in various human tumours based on the TCGA, GEO, and CPTAC databases.…”

Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients

“…Therefore, our data suggest that miR-16-5p can inhibit T cell proliferation by regulating Ca 2+ influx, resulting in the poor recovery of CD4 + T cell counts during ART. Other miRNAs in the panel, such as miR-138-5p, have been reported to be related to immune regulation in tumors and the inflammatory response (84)(85)(86). The expression of miR-323-3p was high in T cells producing inflammatory factors (e.g., interleukin (IL)-17 and IL-22) ( 87), which suggests it may have potential roles in regulating the immune response in HIV infection.…”

Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

“…It has been reported that there is an association between SENP1 expression and cancer immunity, suggesting that SENP1 could be used as a cancer immunotherapy target. SENP1 also correlates with immune infiltration, and a variety of transcription factors involved in regulation of apoptosis, proliferation, cell cycle, tumorigenesis, invasion and metastasis are responsible of the increased expression of SENP1 in cancer cells [ 138 ]. Among them is YY1, which, a few years ago, was shown to form a complex with the chromatin adaptor BRD4 to regulate Senp1 expression [ 139 ].…”

“…SENP1 depletion in multiple myeloma (MM) cells has been shown to decrease viability and proliferation, while inducing apoptosis, which correlates with inactivation of NF-κB signaling [ 103 ]. SENP1 also shows high correlation with sensitivity and resistance to anti-cancer drug and drug targeted genes [ 138 ]. For instance, SENP1 has been shown to reduce cisplatin sensitivity of hypoxic ovarian cancer cells [ 104 ].…”