| 夏海水,王伟,王春梅,等.lncRNA FGD5-AS1通过 miR-133b/PTBP1轴对乳腺癌细胞血管生成的影响机制研究[J].安徽医药,2025,29(7):1336-1341. |
| lncRNA FGD5-AS1通过 miR-133b/PTBP1轴对乳腺癌细胞血管生成的影响机制研究 |
| Mechanism of lncRNA FGD5-AS1 on angiogenesis of breast cancer cells via miR-133b/PTBP1 axis |
| |
| DOI：10.3969/j.issn.1009-6469.2025.07.014 |
| 中文关键词: 乳腺肿瘤 长链非编码 RNA-含有 5个 PH结构域的反义 RNA1 微 RNA-133b 多聚嘧啶区结合蛋白 1 血管生成 |
| 英文关键词: Breast neoplasms LncRNA-lncRNA FGD5-AS1 miR-133b Polypyrimidine tract-binding protein 1 Angiogenesis |
| 基金项目:河北省医学科学研究重点课题计划项目( 20181536) |
| 作者 | 单位 | | 夏海水 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 | | 王伟 | 沧州市人民医院,甲乳外科,河北 沧州 061000 | | 王春梅 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 | | 卢泽芬 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 | | 陈海洋 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 | | 石金升 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 | | 刘金柱 | 沧州市人民医院,肿瘤内科,河北 沧州 061000 |
|
| 摘要点击次数: 915 |
| 全文下载次数: 205 |
| 中文摘要: |
| 目的探讨长链非编码 RNA(LncRNA)-含有 5个 PH结构域的反义 RNA1(FGD5-AS1)通过微 RNA-133b(miR-133b)/多聚嘧啶区结合蛋白 1(PTBP1)轴对乳腺癌细胞血管生成的影响及其机制。方法 2020年 3月至 2023年 6月，利用生物信息学手段探寻了乳腺癌中 lncRNA FGD5-AS1/miR-133b/PTBP1之间可能的互作关系。实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测乳腺癌细胞中 lncRNA FGD5-AS1、miR-133b、PTBP1的表达，细胞增殖与毒性检测试剂盒 -8(CCK-8)和克隆形成检测细胞增殖，蛋白质印迹法检测血管内皮生长因子受体 2(VEGFR-2)、血管内皮生长因子(VEGF)的表达。血管生成实验测定血管生成数量， RIP实验和双萤光素酶实验验证 lncRNA FGD5-AS1与 miR-133b、miR-133b与 PTBP1的结合关系。结果 lncRNA FGD5-AS1在乳腺癌中的表达水平显著高于正常组织［(42.21±5.40)g/L比 28.34±4.20)g/L］其下游 miR-133在乳腺癌中的表达水平显著低于正常组织［(15.12±2.30)g/L比 29.45±3.10)g/L］靶基因 PTBP1在乳腺癌中的表，达水平显著高于正常组织［(65.47±7.20)g/L比 32.14±4.50)g/L］。 RIP实验和双萤光素酶报告结果显示 lncRNA FGD5-AS1与 miR-133b、miR-133b与 PTBP1存在靶向结合关系。实验，细胞实验发现沉默 lncRNA FGD5-AS1能够抑制乳腺癌细胞增殖［观察组 83.17%(84/101)，对照组 95.23%(96/101)］和血管生成能力。在 lncRNA FGD5-AS1被沉默的乳腺癌细胞中，额外进行 miR-133b的沉默或者 PTBP1的过表达，能够有效逆转因 lncRNA FGD5-AS1沉默所导致的细胞增殖减少和血管生成抑制的效果。结论 lncRNA FGD5-AS1通过 miR-133b/PTBP1轴促进乳腺癌血管生成。 lncRNA FGD5-AS1/miR-133b/PTBP1轴调控轴可能成为靶向抑制乳腺癌血管生成的新靶点。 |
| 英文摘要: |
| Objective To investigate the effect and mechanism of long non-coding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) on angiogenesis in breast cancer cells through the microRNA-133b (miR-133b)/polypyrimidine tract-binding protein 1 (PTBP1) axis.Methods This study was conducted from March 2020 to June 2023. Bioinformatics analysis was made to explore the potential in-teractions among lncRNA FGD5-AS1, miR-133b, and PTBP1. The expression levels of lncRNA FGD5-AS1, miR-133b, and PTBP1 in breast cancer cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Western blotting was performed to measure the expressions of vascu-lar endothelial growth factor receptor 2 (VEGFR-2) and vascular endothelial growth factor (VEGF). Angiogenesis was evaluated by tubeformation assays. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were conducted to verify the binding relation-ships between lncRNA FGD5-AS1 and miR-133b, as well as between miR-133b and PTBP1.Results The expression level of lncRNA FGD5-AS1 was significantly higher in breast cancer tissues than in normal tissues [(42.21±5.40) g/L vs. (28.34± 4.20) g/L], while the expression of its downstream target miR-133b was significantly lower in breast cancer tissues [(15.12±2.30) g/L vs. (29.45±3.10) g/L]. Conversely, the expression of PTBP1, a target gene of miR-133b, was significantly higher in breast cancer tissues [(65.47± 7.20) g/L vs. (32.14±4.50) g/L]. RIP and dual-luciferase reporter assays confirmed that lncRNA FGD5-AS1 directly interacts with miR-133b and that miR-133b targets PTBP1. Functional experiments demonstrated that silencing lncRNA FGD5-AS1 inhibited breast cancer cell pro-liferation (treatment group: 83.17%(84/101) vs. control group: 95.23%(96/101) and angiogenesis. Furthermore, additional silencing of miR-133b or overexpression of PTBP1 in lncRNA FGD5-AS1-silenced breast cancer cells effectively reversed the inhibitory effects of lncRNA FGD5-AS1 silencing on cell proliferation and angiogenesis.Conclusions This study demonstrates that lncRNA FGD5-AS1 promotes angiogenesis in breast cancer via the miR-133b/PTBP1 axis. The lncRNA FGD5-AS1/miR-133b/PTBP1 regulatory axis may serve as a novel therapeutic target for inhibiting angiogenesis in breast cancer. |
|
查看全文
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
