Activation of the SIRT1/PGC-1α pathway by HNRNPD promotes vasculogenic mimicry in NSCLC

Lung Cancer is the predominant cause of cancer-related fatalities worldwide, with 80 % classified as non-small cell lung malignancies (NSCLC), characterized by a low 5-year overall survival rate and elevated mortality. Current therapies for NSCLC include targeted drugs, immunotherapy, and combination treatments. The low survival rates highlight the urgent need for novel NSCLC treatments. Vasculogenic mimicry is a tumor blood supply system devoid of endothelium, consisting of invasive and spreading. Heterogeneous Nuclear Ribonucleoprotein D (HNRNPD) expression is upregulated in various cancers. We conducted both in vitro and in vivo experiments by knockdown and overexpression of HNRNPD. Cell proliferation, invasion and angiogenesis were simulated in vitro. A mouse model of subcutaneous transplanted tumor was constructed in vivo, and pathological and immunohistochemical tests were performed.This study examined the involvement of HNRNPD in vasculogenic mimicry in NSCLC and its underlying mechanism. Our research demonstrated that HNRNPD was significantly expressed in NSCLC cells. Inhibition of HNRNPD expression impeded the activation of the Sirtuin 1 / PPARG Coactivator 1 Alpha (SIRT1/PGC-1α) pathway, thereby lowering the proliferation, invasion, and vascular mimicry capability of NSCLC cells. In vivo tests additionally validated that the suppression of HNRNPD could impede tumor growth and angiogenesis in NSCLC murine models. This presents a novel potential target for the targeted therapy of NSCLC. Our research demonstrated that HNRNPD facilitates vasculogenic mimicry development and tumor progression in NSCLC via activating the SIRT1/PGC-1α pathway, offering a novel approach for targeted therapy in NSCLC.

HNRNPD; NSCLC; PGC-1α; SIRT1; Vasculogenic mimicry.