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Published on: July 20, 2019
TNPO1-Mediated Nuclear Import of FUBP1 Contributes to Tumor Immune Evasion by Increasing NRP1 Expression in Cervical
BiKang Yang1, Jing Chen1,2, YinCheng Teng1,2
1Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
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.
Insights
Far upstream element binding protein 1 (FUBP1) promotes cervical cancer (CC) progression by regulating oncogene expression and immune checkpoints. Inhibiting FUBP1 may offer a new therapeutic strategy for CC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Far upstream element binding protein 1 (FUBP1) is a DNA-binding protein involved in oncogenesis.
- The precise mechanisms of FUBP1 in tumor promotion, particularly in cervical cancer, require further investigation.
Purpose of the Study:
- To elucidate the role of FUBP1 in cervical cancer (CC) progression.
- To investigate the molecular mechanisms underlying FUBP1's function in CC.
- To explore FUBP1 as a potential therapeutic target for CC.
Main Methods:
- Analysis of FUBP1 mRNA and protein expression in cervical cancer tissues.
- In vitro functional assays (e.g., knockdown experiments) to assess the impact of FUBP1 on CC cell proliferation and migration.
- Investigation of FUBP1 nuclear localization and its interaction with Transportin-1 (TNPO1).
- Assessment of FUBP1's regulation of immune checkpoint NRP1 gene expression.
Main Results:
- FUBP1 expression is significantly upregulated in cervical cancer and correlates with poor prognosis.
- FUBP1 knockdown inhibits CC cell proliferation and migration, indicating a pro-oncogenic role.
- FUBP1 nuclear translocation, mediated by TNPO1 interaction, regulates the expression of the immune checkpoint NRP1.
- FUBP1 demonstrates a pro-oncogenic function in cervical cancer progression.
Conclusions:
- FUBP1 plays a critical role in cervical cancer progression by regulating oncogene expression and immune checkpoints.
- FUBP1 nuclear localization, facilitated by TNPO1, is a key mechanism in its oncogenic activity.
- FUBP1 represents a promising therapeutic target for restricting cervical cancer progression.
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