PINX1 inhibits proliferation and cisplatin resistance in nasopharyngeal carcinoma by promoting ILF3 ubiquitination.

Abstract

PIN2/TRF1-interacting telomerase inhibitor 1 (PINX1) acts as a tumor suppressor in various cancers, yet its molecular role in nasopharyngeal carcinoma (NPC) remains poorly defined. This study investigates the therapeutic potential of PINX1 in NPC. Expression levels of PINX1 and interleukin enhancer-binding factor 3 (ILF3) were assessed in NPC cells and tissues via western blotting and immunohistochemistry, and their correlation with patient prognosis was analyzed. The effects of ILF3 on NPC cell proliferation and cisplatin resistance were evaluated using cell cycle analysis, EdU incorporation, CCK-8, and IC₅₀ assays. Co-immunoprecipitation and immunofluorescence confirmed the interaction between PINX1 and ILF3, while qPCR and western blotting assessed their regulatory relationship. Bioinformatics analysis, chromatin immunoprecipitation, and dual-luciferase assays were performed to identify transcription factors regulating PINX1. Additional in vitro experiments explored the antagonistic relationship between PINX1 and ILF3. Results showed that PINX1 expression was downregulated in NPC and associated with favorable prognosis, whereas ILF3 was upregulated and linked to poor outcomes. PINX1 physically interacted with ILF3 and promoted its ubiquitination through Speckle-type BTB/POZ protein (SPOP). Furthermore, signal transducer and activator of transcription 3 suppressed PINX1 transcription, while PINX1 antagonized the oncogenic effects of ILF3. Mechanistically, PINX1 facilitated ILF3 degradation via SPOP, suppressed the PI3K-AKT-mTOR pathway, inhibited tumor proliferation, and enhanced cisplatin sensitivity in NPC cells. These findings highlight the tumor-suppressive role of PINX1 and underscore its potential as a therapeutic target in NPC.