LncRNA SNHG12靶向微小RNA-140-3p对氧葡萄糖剥夺/复氧诱导的神经元损伤的保护作用

唐朝1 曹妍群2* 陈超亮3 周菊香3

doi:10.16098/j.issn.0529-1356.2025.06.004

PDF(2808 KB)

解剖学报 ›› 2025, Vol. 56 ›› Issue (6) : 658-663. DOI: 10.16098/j.issn.0529-1356.2025.06.004

神经生物学

LncRNA SNHG12靶向微小RNA-140-3p对氧葡萄糖剥夺/复氧诱导的神经元损伤的保护作用

唐朝¹ 曹妍群^2* 陈超亮³ 周菊香³

作者信息 +

Protective effect of LncRNA SNHG12 on neuronal damage induced by oxygen glucose deprivation/reoxygenation by targeting miR-140-3p

TANG Chao¹ CAO Yan-qun^2* CHEN Chao-liang³ ZHOU Ju-xiang³

Author information +

文章历史 +

摘要

目的探讨长链非编码RNA小核仁RNA宿主基因12（lncRNA SNHG12）靶向微小RNA（miR）-140-3p对氧葡萄糖剥夺/复氧（OGD/R）诱导的神经元损伤的保护作用。方法采用人皮层神经元（HCN）建立OGD/R模型，分为OGD/R组、阴性对照（NC）组、SNHG12组、SNHG12+miR-NC组和SNHG12+miR-140-3p mimics组，另取正常培养的HCN为对照（Ctrl）组，每组共设置6个重复。检测细胞增殖、细胞凋亡、乳酸脱氢酶（LDH）活性、线粒体膜电位、lncRNA SNHG12和miR-140-3p表达水平、lncRNA SNHG12与miR-140-3p的相互作用。结果与对照组相比，OGD/R组HCN存活率、线粒体膜电位、lncRNA SNHG12表达降低（P<0.05），LDH活力、细胞凋亡率、miR-140-3p表达升高（P<0.05）；与OGD/R组和NC组比较，SNHG12组HCN存活率、线粒体膜电位、lncRNA SNHG12表达升高（P<0.05），LDH活力、凋亡率、miR-140-3p表达降低（P<0.05）；与SNHG12+miR-NC组比较，SNHG12+miR-140-3p mimics组HCN存活率、线粒体膜电位降低（P<0.05），LDH活力、凋亡率、miR-140-3p表达升高（P<0.05）；双荧光素酶活性显示，lncRNA SNHG12与miR-140-3p存在靶向关系（P<0.05）。结论 LncRNA SNHG12可能通过抑制miR-140-3p对OGD/R诱导的神经元损伤发挥保护作用。

Abstract

Objective To investigate the protective effect of long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) on neuronal damage induced by oxygen glucose deprivation/reoxygenation (OGD/R) by targeting microRNA (miR)-140-3p. Methods Human cortical neurons (HCN) were used to establish an OGD/R model, which was separated into OGD/R group, negative control (NC) group, SNHG12 group, SNHG12+miR-NC group, and SNHG12+miR-140-3p mimics group. Normal cultured HCN were also taken as the control (Ctrl) group. There were 6 repetitions in each group. Cell proliferation, apoptosis, lactate dehydrogenase (LDH) activity, mitochondrial membrane potential, lncRNA SNHG12 and miR-140-3p expression levels, and the interaction of lncRNA SNHG12 and miR-140-3p were detected. Results Compared with the control group, the survival rate of HCN, mitochondrial membrane potential, and lncRNA SNHG12 expression were lower in the OGD/R group, while the LDH activity, apoptosis rate, and miR-140-3p expression were higher (P<0.05). Compared with the OGD/R group and NC group, the survival rate of HCN, mitochondrial membrane potential, and lncRNA SNHG12 expression were higher in the SNHG12 group, while the LDH activity, apoptosis rate, and miR-140-3p expression were lower (P<0.05). Compared with the SNHG12+miR-NC group, the survival rate of HCN, mitochondrial membrane potential, and lncRNA SNHG12 expression were lower in the SNHG12+miR-140-3p mimics group, while the LDH activity, apoptosis rate, and miR-140-3p expression were higher (P<0.05). Dual luciferase activity showed a targeted relationship between lncRNA SNHG12 and miR-140-3p (P<0.05). Conclusion LncRNA SNHG12 may exert a protective effect against OGD/R-induced neuronal damage by inhibiting miR-140-3p.

导出引用

唐朝曹妍群陈超亮周菊香. LncRNA SNHG12靶向微小RNA-140-3p对氧葡萄糖剥夺/复氧诱导的神经元损伤的保护作用[J]. 解剖学报. 2025, 56(6): 658-663 https://doi.org/10.16098/j.issn.0529-1356.2025.06.004

TANG Chao CAO Yan-qun CHEN Chao-liang ZHOU Ju-xiang. Protective effect of LncRNA SNHG12 on neuronal damage induced by oxygen glucose deprivation/reoxygenation by targeting miR-140-3p[J]. Acta Anatomica Sinica. 2025, 56(6): 658-663 https://doi.org/10.16098/j.issn.0529-1356.2025.06.004

中图分类号： R322.8 R743.31

参考文献

［1］ Abdel-Rahman RF, Alqasoumi SI, Ogaly HA, et al. Propolis ameliorates cerebral injury in focal cerebral ischemia/reperfusion (I/R) rat model via upregulation of TGF-β1［J］. Saudi Pharm J, 2020, 28(1):116-126.

［2］ Wang J, Fu Z, Wang M, et al. Knockdown of XIST attenuates cerebral ischemia/reperfusion injury through regulation of miR-362/ROCK2 axis［J］. Neurochem Res, 2021, 46(8):2167-2180.

［3］ Yang K, Zeng L, Ge A, et al. A systematic review of the research progress of non-coding RNA in neuroinflammation and immune regulation in cerebral infarction/ischemia-reperfusion injury［J］. Front Immunol, 2022, 13:930171.

［4］ Ghafouri-Fard S, Shoorei H, Hussen BM, et al. LncRNA SNHG12: a budding star in human diseases［J］. Pathol Res Pract, 2023, 251(1):154897.

［5］ Wu Y, Huang Y, Cai J, et al. LncRNA SNHG12 improves cerebral ischemic-reperfusion injury by activating SIRT1/FOXO3a pathway through inhibition of autophagy and oxidative stress［J］. Curr Neurovasc Res, 2020, 17(4):394-401.

［6］ Toury L, Frankel D, Airault C, et al. miR-140-5p and miR-140-3p: key actors in aging-related diseases［J］? Int J Mol Sci, 2022, 23(19):11439.

［7］ Mao LY, Liu Y, Tan Zh. The value research of miR-27-3p, miR-128-3p and miR-140-3p expression in the diagnosis and treatment of patients with acute cerebral infarction［J］. Journal of Brain and Nervous Diseases, 2024, 32(1): 39-44. (in Chinese)

毛凌云, 刘洋, 谭政. miR-27-3p、miR-128-3p及miR-140-3p表达在急性脑梗死患者诊疗中的价值研究［J］. 脑与神经疾病杂志, 2024, 32(1): 39-44.

［8］ Ju HY, Tang SS, Li BJ, et al. The expression levels of circulating miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in acute ischemic stroke［J］. Kaohsiung J Med Sci, 2023, 39(9):927-935.

［9］ Zhi SM, Fang GX, Xie XM, et al. Melatonin reduces OGD/R-induced neuron injury by regulating redox/inflammation/apoptosis signaling［J］. Eur Rev Med Pharmacol Sci, 2020, 24(3):1524-1536.

［10］ Yang Y, Jia J, Wei XL, et al. Study on the mechanism of AKT/AMPK/Nrt2 regulated by loganin to improve ferroptosis induced by oxygen glucose deprivation/reoxygenation［J］. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2024, 22(9):1597-1603. (in Chinese)

杨祎, 贾健, 魏小利, 等. 马钱苷调节AKT/AMPK/Nrf2通路改善氧葡萄糖剥夺/复氧诱导的神经元铁死亡的机制研究［J］. 中西医结合心脑血管病杂志, 2024, 22(9):1597-1603.

［11］ Yang YCh, Yang Y, Zhang XL, et al. Hydroxylsafflor yellow A alleviating cerebral ischemia-reperfusion injury in rats by regulating cyclooxygenase-2/ prostaglandin E, signaling pathway［J］. Acta Anatomica Sinica, 2024, 55(4):468-474. (in Chinese)

杨迎春, 杨莹, 张小良, 等. 羟基红花黄色素A通过调控环氧合酶2/前列腺素E2信号通路减轻大鼠脑缺血再灌注损伤［J］. 解剖学报, 2024, 55(4):468-474.

［12］ Sun P, Zhang K, Hassan SH, et al. Endothelium-targeted deletion of microRNA-15a/16-1 promotes poststroke angiogenesis and improves long-term neurological recovery［J］. Circ Res, 2020, 126(8):1040-1057.

［13］ Wang H, Zheng X, Jin J, et al. LncRNA MALAT1 silencing protects against cerebral ischemia-reperfusion injury through miR-145 to regulate AQP4［J］. J Biomed Sci, 2020, 27(1):40.

［14］ Wei R, Zhang L, Hu W, et al. Long non-coding RNA AK038897 aggravates cerebral ischemia/reperfusion injury via acting as a ceRNA for miR-26a-5p to target DAPK1［J］. Exp Neurol, 2019, 314(1):100-110.

［15］ Yan Y, Chen L, Zhou J, et al. SNHG12 inhibits oxygen-glucose deprivation-induced neuronal apoptosis via the miR-181a-5p/NEGR1 axis［J］. Mol Med Rep, 2020, 22(5):3886-3894.

［16］ Yin WL, Yin WG, Huang BS, et al. LncRNA SNHG12 inhibits miR-199a to upregulate SIRT1 to attenuate cerebral ischemia/reperfusion injury through activating AMPK signaling pathway［J］. Neurosci Lett, 2019, 690(1):188-195.

［17］ Ni GX, Duan ChQ, Kou LL, et al. MicroRNA-199a-5p reducing blood-brain barrier disruption following ischemic stroke in rats［J］. Acta Anatomica Sinica, 2024, 55(4):460-467. (in Chinese)

倪广晓, 段春巧, 寇璐璐, 等. 微小RNA-199a-5p保护大鼠脑缺血后血-脑屏障完整性［J］.解剖学报, 2024, 55(4):460-467.

［18］ He J, Xue Y, Wang Q, et al. Long non-coding RNA MIAT regulates blood tumor barrier permeability by functioning as a competing endogenous RNA［J］. Cell Death Dis, 2020, 11(10):936.

［19］ Zhang H, Chen G, Qiu W, et al. Plasma endothelial microvesicles and their carrying miRNA-155 serve as biomarkers for ischemic stroke［J］. J Neurosci Res, 2020, 98(11):2290-2301.

［20］ Song C, Li S, Mai Y, et al. Dysregulated expression of miR-140 and miR-122 compromised microglial chemotaxis and led to reduced restriction of AD pathology［J］. J Neuroinflammation, 2024, 21(1):167.

［21］ Liang S, Ren K, Li B, et al. LncRNA SNHG1 alleviates hypoxia-reoxygenation-induced vascular endothelial cell injury as a competing endogenous RNA through the HIF-1α/VEGF signal pathway［J］. Mol Cell Biochem, 2020, 465(1-2):1-11.

［22］ Zhang Y, Su Q, Xia W, et al. MiR-140-3p directly targets Tyro3 to regulate OGD/R-induced neuronal injury through the PI3K/Akt pathway［J］. Brain Res Bull, 2023, 192(1):93-106.