LncRNA SNHG4 sponges miR-let-7d-5p to drive rare earth-induced pulmonary epithelial-mesenchymal transition via HMGA2.

Epithelial-mesenchymal transition (EMT) is a pivotal biological event in the progression of rare earth pneumoconiosis, and inhibiting EMT represents a critical strategy to reverse or delay this disease. Our previous study revealed that plasma microRNA let-7d (miR-let-7d) levels are significantly lower in patients with rare earth pneumoconiosis than in healthy individuals, yet its role in rare earth-induced EMT remains uncharacterized. Herein, we established a neodymium oxide (Nd2O3) induced pulmonary fibrosis mouse model and found that Nd2O3 exposure triggered pulmonary EMT, accompanied by markedly reduced microRNA let-7d-5p (miR-let-7d-5p) expression and elevated levels of long non-coding RNA SNHG4 (lncRNA SNHG4) and high-mobility group AT-hook 2 (HMGA2). Dual-luciferase reporter assays confirmed that miR-let-7d-5p directly targets both lncRNA SNHG4 and HMGA2. Mechanistically, overexpression of miR-let-7d-5p decreased HMGA2 expression and alleviated Nd2O3-induced EMT. Conversely, knockdown of lncRNA SNHG4 upregulated miR-let-7d-5p, downregulated HMGA2, and mitigated Nd2O3-induced EMT. Collectively, these findings demonstrate that Nd2O3 upregulates lncRNA SNHG4, which acts as a sponge for miR-let-7d-5p to promote HMGA2 expression, thereby driving EMT and subsequent pulmonary fibrosis.