Liu Ming, Wang Denggui, Yan Zhirong, Zhou Min
Department of Anaesthesiology, Fujian Maternity and Child Health Hospital, Fuzhou, China.
Department of Anaesthesiology, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Korean J Pain. 2025 Jul 1;38(3):292-307. doi: 10.3344/kjp.24386. Epub 2025 Jun 25.
Bone cancer pain (BCP), a major symptom impairing quality of life and mobility in cancer patients, is linked to microRNAs dysregulation. This study investigates the role of miR-298 in a mouse BCP model established by implanting tumor cells into the femoral marrow cavity.
Forty-eight male C3H/HeJ mice were randomized into sham or tumor groups, receiving intrathecal miR- 298 agonist/antagonist or controls. Behavioral assessments (paw withdrawal mechanical threshold [PWMT] and number of spontaneous flinches [NSF]) were performed before and after surgery (days 0, 4, 7, 10, 14, 21, 28). Astrocyte activation, inflammatory cytokines, and pathway proteins (MyD88, TAK1, p-p65) were analyzed via quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blot, and immunofluorescence. Statistical analysis used one-way ANOVA with Tukey's test and independent t-tests ( < 0.05).
Tumor-implanted mice showed significant mechanical hypersensitivity in PWMT and NSF versus sham controls ( < 0.001). MiR-298 expression was markedly downregulated in BCP mice ( < 0.001), confirmed by fluorescence in situ hybridization and qRT-PCR. Overexpression of miR-298 suppressed astrocyte proliferation ( = 0.005) and pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β; < 0.001), while enhancing apoptosis ( = 0.003). Luciferase assays confirmed MyD88 as a direct miR-298 target ( < 0.001). Intrathecal miR-298 agonist reduced NF-κB activation (phospho-p65, < 0.001) and alleviated pain behaviors versus tumor controls ( < 0.001).
MiR-298 reduces BCP in mice by inhibiting astrocyte-mediated neuroinflammation and blocking the MyD88/NF-κB pathway.
骨癌痛（BCP）是癌症患者生活质量和活动能力受损的主要症状，与微小RNA失调有关。本研究调查了miR-298在通过将肿瘤细胞植入股骨骨髓腔建立的小鼠BCP模型中的作用。
48只雄性C3H/HeJ小鼠被随机分为假手术组或肿瘤组，接受鞘内注射miR-298激动剂/拮抗剂或对照。在手术前和手术后（第0、4、7、10、14、21、28天）进行行为评估（爪退缩机械阈值[PWMT]和自发退缩次数[NSF]）。通过定量逆转录聚合酶链反应（qRT-PCR）、蛋白质印迹法和免疫荧光分析星形胶质细胞活化、炎性细胞因子和信号通路蛋白（MyD88、TAK1、p-p65）。统计分析采用单因素方差分析和Tukey检验以及独立t检验（P<0.05）。
与假手术对照组相比，植入肿瘤的小鼠在PWMT和NSF方面表现出明显的机械性超敏反应（P<0.001）。荧光原位杂交和qRT-PCR证实，BCP小鼠中miR-298表达明显下调（P<0.001）。miR-298的过表达抑制了星形胶质细胞增殖（P=0.005）和促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β；P<0.001），同时增强了细胞凋亡（P=0.003）。荧光素酶测定证实MyD88是miR-298的直接靶标（P<0.001）。与肿瘤对照组相比，鞘内注射miR-298激动剂可降低NF-κB活化（磷酸化p65，P<0.001）并减轻疼痛行为（P<0.001）。
miR-298通过抑制星形胶质细胞介导的神经炎症和阻断MyD88/NF-κB信号通路减轻小鼠骨癌痛。
