Effect of overexpression of miR-124 on gastric precancerous lesion of model rats based on wnt/ β-catenin signaling pathway
-
摘要:
背景 Wnt/β-catenin信号通路的活跃可以促进胃黏膜细胞的分裂和增长,增加癌变的可能。 目的 探究基于Wnt/β-catenin信号通路过表达miR-124对胃癌前病变模型大鼠的干预效果影响。 方法 选取43只SPF级Wistar大鼠作前瞻性研究,从中选取10只作为对照组(0.9%氯化钠注射液),并将剩余33只大鼠构建胃癌前病变模型,最终建模成功30只,平均分为模型组(0.9%氯化钠注射液)、miR-124抑制剂组(miR-124 inhibitor)和miR-124模拟物组(miR-124 mimic)。 结果 与对照组相比,模型组、miR-124抑制剂组、miR-124模拟物组miR-124相对表达量下降,表皮细胞生长因子(epidermal growth factor,EGF)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、白细胞介素-6(interleukin- 6,IL-6)、肿瘤坏死因子α(tumor necrosis factor,TNF-α)水平以及Wnt、β-catenin表达量升高(P均<0.05);与模型组相比,miR-124抑制剂组miR-124表达水平下降,EGF、EGFR、IL-6、TNF-α水平以及Wnt、β-catenin表达量升高,miR-124模拟物组miR-124相对表达量升高,EGF、EGFR、IL-6、TNF-α水平以及Wnt、β-catenin表达量降低(P均<0.05);与miR-124抑制剂组相比,miR-124模拟物组miR-124相对表达量升高,EGF、EGFR、IL-6、TNF-α水平以及Wnt、β-catenin表达量降低(P均<0.05)。 结论 过表达miR-124可降低大鼠胃黏膜的损害,改善其炎症反应,其机制可能与Wnt/β-catenin信号通路被抑制有关。 -
关键词:
- 胃癌前病变 /
- miR-124 /
- Wnt/β-catenin信号通路 /
- 胃黏膜 /
- 炎症反应
Abstract:Background Active wnt/β-catenin signaling pathway can promote the division and growth of gastric mucosal cells, and increase the possibility of carcinogenesis. Objective To explore the effect of overexpression of miR-124 on precancerous lesions of gastric cancer rats based on wnt/β-catenin signaling pathway. Methods Forty-three SPF Wistar rats were selected for a prospective study, 10 of which were selected as the control group (normal saline), and the remaining 33 rats were used to construct a model of gastric precancerous lesions, with the successful modeling of 30 rats. They were divided into model group (saline), miR-124 inhibitor group and miR-124 simulator group. Results Compared with the control group, the relative expression of miR-124 in the model group, the miR-124 inhibitor group and the miR-124 simulator group decreased, while the epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), interleukin-6 (IL-6), tumor necrosis factor, the levels of TNF-α, wnt and β-catenin were increased (P <0.05); Compared with the model group, the expression level of miR-124 in the miR-124 inhibitor group was decreased, while the expression levels of EGF, EGFR, IL-6, TNF-α, wnt and β-catenin were increased, and the relative expression level of miR-124 in the miR-124 simulator group was also increased. The levels of EGF, EGFR, IL-6, TNF-α, wnt and β-catenin were decreased (all P <0.05). Compared with the miR-124 inhibitor group, the relative expression level of miR-124 in the miR-124 simulator group was increased, while the levels of EGF, EGFR, IL-6, TNF-α, wnt and β-catenin were decreased (all P <0.05). Conclusion Overexpression of miR-124 can reduce the damage of gastric mucosa in rats and improve its inflammatory response. The mechanism may be related to inhibition of wnt/ β- catenin signal pathway. -
Key words:
- pregastric cancer lesions /
- miR-124 /
- Wnt/β-catenin /
- gastric mucosa /
- inflammatory response
-
表 1 各组大鼠肾组织miR-124相对表达量对比
Table 1. Comparison of miR-124 expression in kidney tissues
指标 对照组(n=10) 模型组(n=10) miR-124抑制剂组(n=10) miR-124模拟物组(n=10) F值 P值 miR-124相对表达量 6.82 ± 0.88 2.65 ± 0.43a 1.34 ± 0.15ab 4.94 ± 0.92abc 13.46 <0.001 aP<0.05,vs 对照组; bP<0.05,vs 模型组;cP<0.05,vs miR-124抑制剂组。 表 2 各组大鼠血清标志物水平对比
Table 2. Comparison of serum biomarkers levels in each group
指标 对照组(n=10) 模型组(n=10) miR-124抑制剂组(n=10) miR-124模拟物组(n=10) F值 P值 EGF/(ng·mL-1) 0.69 ± 0.12 3.02 ± 0.29a 4.62 ± 1.03ab 1.48 ± 5.97abc 11.98 <0.001 EGFR/(pg·mL-1) 1.50 ± 0.72 3.41 ± 1.39a 4.95 ± 1.62ab 2.04 ± 6.02abc 6.154 <0.001 IL-6/(pg·mL-1) 31.61 ± 4.25 60.78 ± 6.29a 71.42 ± 7.03ab 42.48 ± 5.07abc 15.32 <0.001 TNF-α/(pg·mL-1) 32.37 ± 4.02 68.41 ± 6.19a 84.05 ± 8.62ab 51.14 ± 6.02abc 17.18 <0.001 aP<0.05,vs 对照组; bP<0.05,vs 模型组;cP<0.05,vs miR-124抑制剂组。 表 3 各组大鼠Wnt/β-catenin通路蛋白表达量对比
Table 3. Comparison of wnt / β -catenin pathway protein expression in rats
指标 对照组(n=10) 模型组(n=10) miR-124抑制剂组(n=10) miR-124模拟物组(n=10) F值 P值 Wnt 1.00 ± 0.01 3.02 ± 0.49a 4.85 ± 0.55ab 1.81 ± 0.32abc 6.538 <0.001 β-catenin 1.00 ± 0.01 3.57 ± 0.48a 4.76 ± 0.59ab 2.03 ± 0.21abc 9.295 <0.001 aP<0.05,vs 对照组; bP<0.05,vs 模型组;cP<0.05,vs miR-124抑制剂组。 -
[1] 王郅宜,赵鲁卿,李丹艳. 张声生从毒瘀互结论治胃癌前病变[J]. 环球中医药,2022,15(4): 622-625. doi: 10.3969/j.issn.1674-1749.2022.04.014 [2] Gullo I,Grillo F,Mastracci L,et al. Precancerous lesions of the stomach,gastric cancer and hereditary gastric cancer syndromes[J]. Pathologica,2020,112(3): 166-185. doi: 10.32074/1591-951X-166 [3] 李志云,王捷虹,杨燕燕,等. 沈舒文辨治胃癌前病变临床经验采撷[J]. 吉林中医药,2022,42(4): 408-412. [4] Zhang Y,Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer[J]. J Hematol Oncol,2020,13(1): 165. doi: 10.1186/s13045-020-00990-3 [5] 王艺臻,王佳林,朱西杰. 基于PI3K/AKT/mTOR信号通路研究复方蜥蜴散凝胶对胃癌前病变模型大鼠的调控作用[J]. 中医学报,2021,36(10): 2154-2158. [6] Zhang P,Yang MR,Zhang YD,et al. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer[J]. Cell Rep,2020,30(12): 4317. doi: 10.1016/j.celrep.2020.03.020 [7] Eusebi LH,Telese A,Marasco G,et al. Gastric cancer prevention strategies:a global perspective[J]. J Gastroenterol Hepatol,2020,35(9): 1495-1502. doi: 10.1111/jgh.15037 [8] 黄文静,陈克河. REG Ⅳ、ORP150与miRNA-223联合检测对胃癌的诊断价值[J]. 实用癌症杂志,2022,37(4): 630-633. doi: 10.3969/j.issn.1001-5930.2022.04.029 [9] 陶正贵,杜静虎,田葵,等. hsa-miR-124-3p. 1靶向TRAF6抑制人胃癌细胞的迁移和侵袭[J]. 西安交通大学学报(医学版),2021,42(6): 843-849. [10] 罗远,蒋海忠. miR-124通过调控PI3K/Akt信号通路对人胃癌MGC803细胞增殖与凋亡的影响[J]. 浙江临床医学,2020,22(10): 1407-1410. [11] 张晓玲,袁蒲,张征波,等. 血清miR-124和miR-20a联合检测对胃癌的诊断价值研究[J]. 现代消化及介入诊疗,2019,24(11): 1344-1347. doi: 10.3969/j.issn.1672-2159.2019.11.032 [12] 符清胜,吴克盛,赵军,等. miR-124对胃癌细胞的生物学功能影响[J]. 皖南医学院学报,2019,38(5): 414-418. doi: 10.3969/j.issn.1002-0217.2019.05.002 [13] 王允,申重阳,韩建军,等. 胃癌并发Hp感染患者血清miR-101,HSP-70,IL-1β表达水平与肿瘤增殖和侵袭力的相关性研究[J]. 现代检验医学杂志,2022,37(2): 17-22. doi: 10.3969/j.issn.1671-7414.2022.02.004 [14] 韦维,黄海舸,陆佳明,等. microRNA-124对胃癌细胞增殖与凋亡的影响及其与PI3K/Akt信号通路的关系[J]. 中国普通外科杂志,2020,29(6): 723-730. doi: 10.7659/j.issn.1005-6947.2020.06.013 [15] 董守森,尚延生. 幽门螺杆菌相关性胃疾病中miR-551b和miR-124a的表达及意义[J]. 中国微生态学杂志,2022,34(2): 201-205. [16] Qu Y,Wang XH,Bai S,et al. The effects of TNF-α/TNFR2 in regulatory T cells on the microenvironment and progression of gastric cancer[J]. Int J Cancer,2022,150(8): 1373-1391. doi: 10.1002/ijc.33873 [17] 陈炜聪,文彬,孙海涛,等. 鳖甲煎丸对二乙基亚硝胺诱导的肝癌前病变模型大鼠肝组织IL-6/STAT3信号通路的影响[J]. 中医杂志,2021,62(19): 1720-1727. [18] 郭敏,王晓鸽,杨国红,等. 健脾活瘀方抑制IL-6/JAK1/STAT3信号通路抗胃癌前病变的机制研究[J]. 中医药信息,2020,37(3): 44-49. [19] 于春月,李依聪,苏泽琦,等. 慢痞消对慢性萎缩性胃炎大鼠血清炎症指标IL-1β、IL-6和TNF-α表达水平的影响[J]. 中华中医药杂志,2019,34(5): 1979-1983. [20] 马建,王新军,付旭东,等. miR-124靶向STAT3改善脑恶性胶质瘤细胞辐射敏感性[J]. 中华放射医学与防护杂志,2019,39(2): 88-94. doi: 10.3760/cma.j.issn.0254-5098.2019.02.002 [21] 边春红,梁乐,王永刚,等. 血清胃蛋白酶原联合肿瘤坏死因子-α检测在幽门螺杆菌相关性胃疾病诊断中的意义[J]. 西部医学,2020,32(7): 1071-1075. [22] 郑轶,刘颜敏,陈志涛,等. 幽门螺杆菌感染的胃癌和癌前病变组织中肿瘤坏死因子-α的表达及临床意义[J]. 临床内科杂志,2020,37(10): 718-720. doi: 10.3969/j.issn.1001-9057.2020.10.013 [23] 吕小燕,冯五金,李军祥. 基于Wnt/β-catenin信号角度的珍珠舌草胶囊治疗胃息肉的分子机制探究[J]. 时珍国医国药,2021,32(2): 366-368. doi: 10.3969/j.issn.1008-0805.2021.02.32 [24] 许媛媛,王晨,贺赞,等. MAGEA1通过激活Wnt/β-catenin信号通路促进恶性黑色素瘤的转移[J]. 解放军医学院学报,2021,42(2): 182-188,196. [25] 康建媛,张竞超,李燕君,等. 基于血清胃功能3项及Wnt/β-catenin信号通路相关蛋白探索萎胃颗粒对胃癌前病变患者的作用[J]. 中国中西医结合消化杂志,2020,28(8): 613-616. doi: 10.3969/j.issn.1671-038X.2020.08.09 -