RAN directly binds and stabilizes G3BP1 mRNA in the nucleus to facilitate proliferation and metastasis of nasopharyngeal carcinoma (si-G3BP1 RNA-seq)

RNA binding proteins (RBPs) play a critical role in tumor progression by participating in the post-transcriptional regulation of RNA. However, the expression and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. This study identified 5 RBPs (RAN, EZH2, RDM1, HRSP12, and ALYREF) that were up-regulated in NPC and could promote NPC cells migration or proliferation. RAN was first investigated because of its most significant effect on NPC cells. Functionally, RAN facilitated NPC proliferation, migration, and invasion in vitro and in vivo. High expression of RAN was associated with poor prognosis of NPC patients and could be performed as a prognostic biomarker. Mechanistically, RAN mediated the nucleus import of TDP43 and enhanced TDP43 nuclear distribution. On the other hand, RAN was directly bound to the coding sequence of G3BP1 mRNA and served as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3’untranslated region. Thereby increased G3BP1 mRNA stability in the nucleus and led to up-regulation of G3BP1, which further enhanced ATK/ERK phosphorylation and ultimately promoted NPC proliferation and metastasis. RNA-seq was performed to search downstream pathway regulated by G3BP1, G3BP1 was knocked down by siRNA in HONE-1 cells and total RNA from G3BP1 silenced or control HONE-1 cells were extracted. Gene expression profiling analysis was performed using data from RNA-seq of si-G3BP1 and control HONE-1 cells.