RBM4 Promotes Nasopharyngeal Carcinoma Growth and Metastasis by Stabilizing HOXB13 mRNA.

Abstract

Nasopharyngeal carcinoma (NPC) remains a major clinical challenge, particularly at advanced stages. RNA-binding proteins (RBPs) are important post-transcriptional regulators of tumorigenesis, but their roles in NPC remain poorly understood. This study investigated whether RNA-binding motif protein 4 (RBM4) stabilizes homeobox B13 (HOXB13) mRNA and thereby activates oncogenic signaling to promote NPC progression. Bioinformatics analysis identified differentially expressed genes in NPC. ENCORI was used to predict potential RNA-binding proteins (RBPs) targeting the candidate gene, and the predicted interaction was validated by RNA immunoprecipitation. Functional effects of HOXB13 and RBM4 in NPC cells were examined using colony formation and Transwell assays, along with modulating RBM4, HOXB13, nuclear factor kappa B (NF-κB) p65, and β-catenin expression. In vivo, effects of the RBM4/HOXB13 axis on NPC tumor growth and metastasis were evaluated using murine xenograft and lung metastasis models. HOXB13 was among the most strongly upregulated genes in NPC, and RBM4 was predicted to be a candidate RBP targeting HOXB13 mRNA. RBM4 was also upregulated in NPC models and increased HOXB13 mRNA stability. RBM4 silencing suppressed NPC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while increasing apoptosis and reducing HOXB13 expression and NF-κB and Wnt/β-catenin signaling. Overexpression of HOXB13, NF-κB p65, or β-catenin partially reversed these effects. In vivo, RBM4 silencing inhibited xenograft growth and experimental lung metastasis, and these effects were partially reversed by HOXB13 overexpression. RBM4 acts as a pro-tumorigenic RBP in NPC by stabilizing HOXB13 mRNA and activating the NF-κB and Wnt/β-catenin pathways. The RBM4/HOXB13 axis therefore warrants further investigation as a potential molecular target in NPC.