Long noncoding RNA NONRATT007487.2 drives cancer-induced bone pain progression through direct interaction with CXCL1

Abstract

Background: Cancer-induced bone pain (CIBP) is a significant and challenging comorbidity closely related to cancer metastasis. Long noncoding RNAs (lncRNAs) have been implicated in both cancer progression and pain modulation, however, their specific role in CIBP remains unclear. The present study aims to elucidate the potential mechanisms by which lncRNA NONRATT007487.2 contributes to the development of CIBP. Methods: A CIBP model was established by injecting Walker 256 mammary gland tumor cells into the tibial canal of rats. To assess cancer-induced pain behavior, the authors measured the paw withdrawal threshold and paw withdrawal latency. Transcriptome sequencing was conducted to identify the pathways and genes regulated by lncRNA NONRATT007487.2. Additionally, immunofluorescence, RNA fluorescence in situ hybridization (FISH), and RNA pulldown assays were performed to investigate the relationship between lncRNA NONRATT007487.2 and C-X-C motif chemokine ligand 1 (CXCL1). Results: It was observed that lncRNA NONRATT007487.2 was significantly upregulated in the spinal cords of CIBP rats. Knockdown of lncRNA NONRATT007487.2 alleviated both mechanical and thermal hyperalgesia in these rats and appeared to inhibit the chemokine signaling pathway. Notably, CXCL1 expression was notably reduced following the loss of lncRNA NONRATT007487.2. FISH assays demonstrated co-location of lncRNA NONRATT007487.2 and CXCL1 in the spinal cord, and RNA pulldown assays confirmed the direct interaction between these two molecules. Conclusions: The results indicated that lncRNA NONRATT007487.2 plays a crucial regulatory role in CIBP through its interaction with CXCL1, presenting a potential therapeutic target for alleviating nociceptive hypersensitivity associated with bone metastasis.