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M⁶A-Dependent Interaction Between circSMAD2 and IGF2BP2 Upregulates SMAD2 and Drives Nasopharyngeal Carcinoma Progression

ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck, with tumor recurrence and distant metastasis being major contributors to poor patient prognosis. However, the underlying molecular mechanisms remain incompletely understood. Circular RNAs (circRNAs) have emerged as important regulators in NPC progression. In this study, we identified circSMAD2 as significantly upregulated in NPC tissues, with high expression correlating with poor clinical outcomes. Functional assays in vitro and in vivo demonstrated that circSMAD2 promotes NPC cell invasion and lung colonizationmetastasis. Mechanistically, circSMAD2 binds to IGF2BP2 and facilitates its nuclear export in an m⁶A-dependent manner, facilitating IGF2BP2’s recognition of m⁶A modification sites on SMAD2 mRNA, thereby increasing SMAD2 mRNA stability and expression. The elevated SMAD2 subsequently activates key epithelial-mesenchymal transition (EMT) regulators ZEB1 and TWIST, promoting NPC cell invasiveness and metastatic potential. This study identifies a previously uncharacterized role of circSMAD2 in NPC and suggests that it may regulate the parental gene SMAD2 via m⁶A modification. These results contribute to understanding NPC biology and may inform future therapeutic strategies.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: 佳蓉张

LAB HEAD: Jiarong, Zhang

PROVIDER: PXD069167 | Pride | 2025-10-10

REPOSITORIES: pride

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			Action	DRS
	RE599GI_biotin.raw	Raw
	RE599GI_biotin_MS_identified_information.xlsx	Xlsx
	RE599GI_unbiotin.raw	Raw
	RE599GI_unbiotin_MS_identified_information.xlsx	Xlsx
	checksum.txt	Txt

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