Importin 7 Mediated Nuclear Transport of MSI2 as a Therapeutic Target in Cervical Cancer

Abstract Cervical cancer (CC) remains a significant health threat to women worldwide, with a pressing need for novel therapeutic targets. Despite recent advances, the molecular mechanisms underlying CC progression are not fully understood. Nuclear transport proteins, key regulators of macromolecule movement between cellular compartments, have emerged as potential targets in cancer therapy. However, the specific role of Importin 7 (IPO7) in CC development and its clinical implications remain poorly characterized, indicating a significant gap in our current understanding. Here, we investigated IPO7's role in CC, leveraging clinical samples, bioinformatics analyses from TCGA and GEO databases, and experimental models. We found that IPO7 is upregulated in CC and associated with poor prognosis. IPO7 knockdown in cell lines and animal models revealed decreased cell proliferation, reduced colony formation, inhibited migration and invasion, and enhanced apoptosis. To uncover IPO7's molecular mechanisms, we performed mass spectrometry analysis, identifying MSI2, an RNA-binding protein, as a potential cargo. Further validation confirmed a direct interaction between IPO7 and MSI2, with IPO7 overexpression coupled with MSI2 knockdown abrogating oncogenic effects. Sequencing analysis of IPO7-knockdown cells indicated the MYC targets pathway and co-immunoprecipitation assays confirmed a direct interaction between MYC and MSI2, suggesting that IPO7 may facilitate the nuclear transport of MSI2 and MYC, thereby promoting cancer progression. Clinically, elevated MSI2 expression in CC patients, particularly in advanced stages, correlated with poorer outcomes. Our findings elucidate the role of IPO7 in CC, demonstrating its potential as a therapeutic target. The interaction between IPO7, MSI2, and MYC provides a novel avenue for developing targeted therapies. Importantly, our results underscore the importance of IPO7-mediated nuclear transport in CC progression, presenting a promising strategy for enhancing patient outcomes and advancing CC treatment.