LncRNA NONRATT014888.2 contributes to cancer-induced bone pain through downregulation of natriuretic peptide receptor 3 in rats

• Published in: Biochemical and biophysical research communications 2023-11, Vol.683, p.149114-149114, Article 149114
• Main Authors: Dou, Qianshu, Ba, Futing, Hu, Shufen, Xu, Guang-Yin, Wei, Jinrong, Jiang, Guo-Qin
• Format: Article
• Language: English
• Subjects: Cancer-induced bone pain; carcinogenesis; cytoplasm; Dorsal root ganglion; females; hypersensitivity; intrathecal injection; lncRNA NONRATT014888.2; mammary glands; Natriuretic peptide receptor 3; natriuretic peptide receptors; neoplasms; non-coding RNA; pain; Pain pathway; protein content; somatosensory disorders; tibia
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2023.10.046

Long noncoding RNA (lncRNA) is implicated in both cancer development and pain process. However, the role of lncRNA in the development of cancer-induced bone pain (CIBP) is unclear. LncRNA NONRATT014888.2 is highly expressed in tibia related dorsal root ganglions (DRGs) in CIBP rats which function is unknown. CIBP was induced by injection of Walker 256 mammary gland tumor cells into the tibia canal of female SD rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. Down-regulation of NONRATT014888.2 by siRNA in CIBP rats markedly attenuated hind-paw mechanical pain hypersensitivity. LncRNA-predicted target mRNAs analysis and mRNA sequencing results cued Socs3, Npr3 were related with NONRATT014888.2. Intrathecal injection of NONRATT014888.2-siR206 upregulated Npr3 both in mRNA and protein level. Npr3 was co-expressed in NONRATT014888.2-positive DRGs neurons and mainly located in cytoplasm, but not in Glial fibrillary acidic protein (GFAP)-positive cells. Intrathecal injection of ADV-Npr3 upregulated Npr3 expression and enhanced the PWT of CIBP rats. Our results suggest that upregulated lncRNA NONRATT014888.2 contributed to hyperalgesia in CIBP rats, and the mechanism may through downregulation of Npr3. •Upregulation of lncRNA NONRATT014888.2 showed tibia specificity.•lncRNA NONRATT014888.2 contributed to mechanical hyperalgesia.•lncRNA NONRATT014888.2 co-located with Npr3 in cytoplasm of neurons.•Inhibition of lncRNA NONRATT014888.2 effectively increased Npr3 expression.