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长链非编码RNA DBH-AS1通过下调AKT1表达抑制胰腺癌进展 |
李慧芬1, 程文英2, 陶元平1, 杨乐1, 欧阳柳3, 李小玲2, 汪珍光1, 曹晶珠4
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1.海军军医大学第三附属医院肝外三科, 上海 200433;2.中国人民解放军 92493 部队医院内三科, 葫芦岛 125003;3.海军军医大学第一附属医院普外三科, 上海 200433;4.海军军医大学第一附属医院内分泌科, 上海 200433
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摘要: |
目的 检测长链非编码RNA DBH-AS1在胰腺癌中的表达情况,探讨DBH-AS1在胰腺癌进展中潜在的分子作用。方法 选择2015年7月至2017年12月海军军医大学第一附属医院普外三科收治的原发胰腺癌患者45例,收集患者经手术切除的胰腺癌组织和对应癌旁组织。利用在线数据库GEPIA分析DBH-AS1在胰腺癌肿瘤组织的表达情况。采用实时荧光定量PCR检测DBH-AS1在胰腺癌肿瘤组织及胰腺癌细胞系中的表达水平。分别通过CCK-8实验、克隆形成实验和transwell实验,检测DBH-AS1对胰腺癌细胞增殖、克隆形成和迁移侵袭能力的影响。采用Western印迹法测定蛋白质水平。结果 GEPIA数据库和定量PCR结果显示,与癌旁正常胰腺组织相比,DBH-AS1在胰腺癌组织中表达水平下调,差异有统计学意义(P<0.05)。在胰腺癌肿瘤组织中DBH-AS1的低表达与肿瘤分化差(P=0.038)、TNM分期晚期(P=0.029)、淋巴结转移(P=0.006)以及预后不良(短无瘤生存时间和总体生存时间,P<0.05)有关。DBH-AS1基因敲低可促进胰腺癌细胞的增殖、克隆形成,增强其迁移和侵袭能力,与对照组差异均有统计学意义(P<0.05)。机制研究表明,在胰腺癌中,DBH-AS1通过下调AKT1表达水平,抑制mTOR信号通路。结论 DBH-AS1能通过降低AKT1的表达抑制胰腺癌的进展。 |
关键词: AKT1 细胞侵袭 细胞增殖 胰腺癌 长链非编码RNA |
DOI:10.12025/j.issn.1008-6358.2022.20210070 |
分类号:R735.9 |
基金项目:国家重点研发计划(2018YFC1004900,2018YFC1005002). |
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Long non-coding RNA DBH-AS1 inhibits pancreatic cancer progression via down-regulation of AKT1 expression |
LI Hui-fen1, CHENG Wen-ying2, TAO Yuan-ping1, YANG Le1, OUYANG Liu3, LI Xiao-ling2, WANG Zhen-guang1, CAO Jing-zhu4
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1.Department of the Third Branch of Extrahepatic, the Third Affiliated Hospital of Naval Medical University, Shanghai 200433, China;2.Department of the Third Branch of Internal Medicine, 92493 Military Hospital, Huludao 125003, Liaoning, China;3.Department of the Third Branch of General Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai 200438, China;4.Department of Endocrine, the First Affiliated Hospital of Naval Medical University, Shanghai 200438, China
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Abstract: |
Objective To determine the expression of long non-coding RNA DBH-AS1 in pancreatic cancer and to explore the potential molecular effects of DBH-AS1 on mediating pancreatic cancer progression. Methods From July 2015 to December 2017, 45 patients with primary pancreatic cancer were selected from the Third Department of General Surgery, the First Affiliated Hospital of Naval Medical University. Pancreatic cancer tissues and corresponding adjacent tissues were collected. The expression of DBH-AS1 in pancreatic cancer tissue was analyzed in GEPIA database. DBH-AS1 expression was detected by quantitative real-time polymerase chain reaction (PCR). Cell proliferation, migration, and invasion were detected by CCK-8, colony formation, and transwell assays, respectively. Protein levels were measured by Western blotting. Results DBH-AS1 expression was decreased in cancerous tissues from pancreatic cancer patients (P<0.05). Low expression of DBH-AS1 was associated with poor differentiation (P=0.038), advanced TNM stage (P=0.029), lymph node metastasis (P=0.006), and poor prognosis (shorter tumor-free survival time and overall survival time, P<0.05). DBH-AS1 knockdown promoted the proliferation and clone formation of pancreatic cancer cells and enhanced their migration and invasion capabilities (P<0.05). Mechanism studies revealed that DBHAS1 inhibited mTOR pathway by decreasing AKT1 expression. Conclusion DBH-AS1 inhibits pancreatic cancer progression via down-regulation of AKT1 expression. |
Key words: AKT1 cell invasion cell proliferation pancreatic cancer long non-coding RNA |