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

Bikang Yang,Yincheng Teng,Jing Chen,Jian Song

doi:10.1155/2021/9994004

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.

Highlights

Far upstream element binding protein 1 (FUBP1) is an important regulator of transcription and translation that exerts its function by binding to the distal far upstream element (FUSE) [1]
The genetic overexpression of FUBP1 was demonstrated in a multitude of cancers by comparing pan-cancer gene expression, such as cervical cancer (CC), which indicates that FUBP1 may act as an oncogene (Figure 1(a))
We speculated that FUBP1 is a particular prooncogenic gene that selectively contributes to the progression of CC

Summary

Introduction

FUBP1 (far upstream element binding protein 1) is an important regulator of transcription and translation that exerts its function by binding to the distal far upstream element (FUSE) [1]. Given that the nuclear localization of FUBP1 crucially affects the transcription of oncogenes, we speculated that blocking the nuclear import of FUBP1 suppresses cancer proliferation and becomes a potential target for cancer therapy. To further understand the complex tissue microenvironment (TME) under pathophysiological conditions, such as tumor TME, it is important to analyze immune checkpoint proteins and phenotypic markers. Classical immune checkpoint proteins PD-1 and CTLA-4 are upregulated in tumor-infiltrating T cells, and checkpoint blockade immunotherapy established a new approach in cancer treatment [9, 10]. As an unidentified immune checkpoint in T cells, blocking Neuropilin-1 (NRP1) can improve immunotherapy and prevent cancer recurrence [11]. NRP1 is upregulated in Treg cells of cancer patients, suggesting that it may be a novel target of cancer immunotherapy

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