Work

MIAT-DHX9 spatiotemporal expression drives venous neointimal hyperplasia through nucleolar homeostasis and mitotic progression

Year: 2025

Type: article

Abstract: Venous neointimal hyperplasia, characterized by abnormal smooth muscle cell (SMC) proliferation, represents a critical contributor to stenosis and therapeutic failure following vascular interventions. Here, we identified spatiotemporal nucleolar expression of DExH-box helicase 9 (DHX9) and its binding partner, long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT), using multi-super-resolution imaging and single-molecule fluorescence in situ hybridization (FISH). In normal SMCs, DHX9 transiently localized to nucleoli during the early S phase. CRISPR-mediated MIAT activation facilitated DHX9's nucleolar localization and interaction with PARP1. MIAT also drove SMC proliferation by accelerating cell cycle progression. Depleting MIAT or DHX9 led to nucleolar disorganization, mitotic defects, and DNA damage. Using deep learning, we identified nucleolar-associated morphological features as potential biomarkers for cellular status and disease progression. In an ex vivo and animal model, knockdown of MIAT-DHX9 suppressed SMC proliferation and intimal hyperplasia. Our findings establish the MIAT-DHX9 axis as a central regulator of SMC nucleolar homeostasis and mitotic progression, offering a nucleolus-centered strategy to suppress neointimal hyperplasia.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116578