Abstract：
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.
摘要：
长链非编码RNA（lncRNA）与癌症发展和疼痛过程有关。然而,lncRNA在癌症诱导的骨痛(CIBP)中的作用尚不清楚.LncRNANONRATT014888.2在CIBP大鼠的胫骨相关背根神经节（DRGs）中高表达，功能未知。雌性SD大鼠胫骨管注射Walker256乳腺肿瘤细胞诱导CIBP。测量大鼠的爪退缩阈值（PWT）和爪退缩潜伏期（PWL）。siRNAinCIBP大鼠下调NONRATT014888.2后爪机械性疼痛超敏反应。LncRNA预测的靶mRNA分析和mRNA测序结果提示Socs3，Npr3与NONRATT014888.2相关。鞘内注射NONRATT014888.2-siR206在mRNA和蛋白质水平均上调Npr3。Npr3在NONRATT014888.2阳性DRGs神经元中共表达，主要位于细胞质中，但不在胶质纤维酸性蛋白（GFAP）阳性细胞中。鞘内注射ADV-Npr3上调Npr3表达并增强CIBP大鼠的PWT。我们的结果表明，上调的lncRNANONRATT014888.2有助于CIBP大鼠的痛觉过敏，其机制可能是通过下调Npr3。
