TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical Cancer

Abstract

Far upstream element binding protein 1 (FUBP1), a DNA-binding protein, participates in diverse tumor-promoting behaviors by regulating the expression of oncogenes in the nucleus, but the underlying mechanisms remain to be elucidated. In the present study, we found that FUBP1 mRNA and protein expressions were markedly upregulated and closely linked with poor prognosis in cervical cancer. In vitro, functional experiments showed that knockdown of FUBP1 inhibited CC cell proliferation and migration. Therefore, FUBP1 plays a prooncogenic function in CC progression. Further investigations for the first time demonstrated that nuclear localization of FUBP1 regulated the gene expression of immune checkpoint NRP1. Moreover, our work demonstrated that FUBP1 translocated into the nucleus which was mediated by interacting with Transportin-1 (TNPO1). Collectively, this study revealed that FUBP1 might be a potential therapeutic target for the restriction of tumor progression.

Far upstream element‐binding protein 1 confers lobaplatin resistance by transcriptionally activating PTGES and facilitating the arachidonic acid metabolic pathway in osteosarcoma

“…Recently, it was reported that FUBP1 could interact with some noncoding RNAs and promote tumorigenesis in lung cancer and breast cancer by activating the proto‐oncogene MYC 15,33 . Additionally, nuclear import of FUBP1 could contribute to tumor immune evasion in cervical cancer 34 . In osteosarcoma, we found that FUBP1 was upregulated and that overexpression of FUBP1 promoted drug resistance to lobaplatin.…”

“… 15 , 33 Additionally, nuclear import of FUBP1 could contribute to tumor immune evasion in cervical cancer. 34 In osteosarcoma, we found that FUBP1 was upregulated and that overexpression of FUBP1 promoted drug resistance to lobaplatin. According to the ChIP‐seq and RNA‐seq data, FUBP1 bound to the promoter of PTGES, promoting transcription.…”

In vivo Safety and Immunoactivity of Oncolytic Jurona Virus in Hepatocellular Carcinoma: A Comprehensive Proteogenomic Analysis

“…In the associated DEGs/DEPs, we identified the top 30 enriched features that were significantly upregulated or downregulated in the JURV group compared to the control group (PBS). Among the upregulated features, the S1pr3 38 , Tnpo1 39 , Psmb10 40 , Ddt 41 , Ncor2 42 , Slc04c1 43 have been identified in inflammation, host immune response against microorganisms (virus, bacteria) and tumorigenesis.…”

Systematic pan‐cancer analysis identified neuropilin 1 as an immunological and prognostic biomarker

“…Kaplan–Meier survival analysis using TCGA data revealed that high expression of NRP1 was associated with poor prognosis for OS, DSS, DFI, and PFI in patients with ACC and CESC. An in vitro study 17 showed that far upstream element binding protein 1 (FUBP1) promoted cervical cancer cell proliferation by regulating the expression of the NRP1 gene through localization, which suggested that NRP1 may act as an oncogene during cervical carcinogenesis. Our study found that NRP1 expression in most tumors was independent of tumor stage, and a few differed significantly between stages I and II.…”

“…Kaplan-Meier survival analysis using TCGA data revealed that high expression of NRP1 was associated with poor prognosis for OS, DSS, DFI, and PFI in patients with ACC and CESC. An in vitro study 17 showed that far upstream element binding protein 1 (FUBP1) promoted cervical As it is well established that tumors with high somatic mutation rates can produce new tumor antigens and thus become new targets for cancer immunotherapy, TMB has shown great value as a reasonable indicator to measure the number of genomic mutations 11 and as a predictive biomarker. Previous studies have shown 19 that a high TMB combined with a low copy number has a good predictive effect on immune checkpoint inhibitor efficacy.…”