Feiyanning formula inhibits metastasis and differentiation of osteoclasts by targeting miR-328/NF-κB signaling axis via exosomal HOTAIR in lung cancer cells

As one of the most lethal malignant tumors worldwide, the highly invasive and metastatic nature of lung cancer leads to a generally poor prognosis for patients. Among the complications associated with lung cancer, skeletal-related events (SREs) resulting from bone metastases, including bone pain, pathological fractures, hypercalcemia, and spinal cord compression, significantly impair quality of life and reduce survival rates. The long non-coding RNA HOTAIR, which has been linked to various cancers, plays an unclear role in lung cancer bone metastasis and the regulation of the immune microenvironment. In this study, we investigated the expression of HOTAIR in non-small cell lung cancer (NSCLC) and its impact on the immune microenvironment using bioinformatics, microscopy, and functional assays. Our findings indicate that elevated HOTAIR expression is associated with poorer prognosis based on transcriptomic analyses. Bioinformatics validation in independent GEO datasets and clinical tissue samples also confirmed the prognostic value of HOTAIR in NSCLC bone metastasis subgroups. Mechanistically, HOTAIR expression was correlated with alterations in immune cell infiltration patterns, including reduced B-cell and CD8+ T-cell signatures, and was accompanied by increased NF-κB and ERBB pathway activity. These observations suggest that exosome-associated HOTAIR may influence tumor progression-related processes and osteoclast-associated events relevant to bone metastatic progression. Furthermore, the Feiyanning formula (FYN) demonstrated inhibitory effects on tumor growth and metastasis-related phenotypes in experimental models.