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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2021, Vol. 10 ›› Issue (06): 629 -635. doi: 10.3877/cma.j.issn.2095-3232.2021.06.020

基础研究

miR-429在胰腺导管腺癌患者预后中的价值及作用机制
朱倩1, 陈怡然1, 侍超2, 沈晶尧2, 徐亮2, 应杰2, 胡立平2,†()   
  1. 1. 430071　武汉大学中南医院肝胆胰外科
    2. 211700　江苏省淮安市盱眙县人民医院普通外科
  • 收稿日期:2021-08-20 出版日期:2021-09-23
  • 通信作者: 胡立平
  • 基金资助:
    国家自然科学青年科学基金(82002589); 武汉大学中南医院优博基金项目(ZNYB2019007); 武汉大学青年教师资助项目(2042020kf0145)

Value and mechanism of miR-429 in clinical prognosis of patients with pancreatic ductal adenocarcinoma

Qian Zhu1, Yiran Chen1, Chao Shi2, Jingyao Shen2, Liang Xu2, Jie Ying2, Liping Hu2,†()   

  1. 1. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
    2. Department of General Surgery, Xuyi People's Hospital, Huai'an 211700, China
  • Received:2021-08-20 Published:2021-09-23
  • Corresponding author: Liping Hu
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目的

探讨miR-429在胰腺导管腺癌（PDAC）患者预后中的价值及作用机制。

方法

回顾性分析2015年6月至2019年8月在江苏盱眙县人民医院诊治的95例PDAC患者临床病理资料。患者均签署知情同意书，符合医学伦理学规定。其中男60例，女35例；年龄32~76岁，中位年龄61岁。实时荧光定量RT-PCR检测患者miR-429表达，分析miR-429表达与患者生存预后的关系。细胞实验采用人胰腺癌细胞系Bxpc-3和Panc-1，分别采用MTT法和Transwell法检测细胞增殖和迁移能力。免疫荧光染色检测上皮-间质转化（EMT）相关因子E-cadherin、N-cadherin和vimentin表达。两组miR-429相对表达量比较采用t检验，miR-429表达与PDAC患者临床病理特征的关系分析采用χ2检验。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

PDAC患者肿瘤组织miR-429平均相对表达量为1.02±0.43，明显低于癌旁正常组织的2.35±0.27（t=-1.732，P<0.05）。miR-429表达与TNM分期和肿瘤血管侵犯相关（χ2=3.877，2.584；P<0.05）。miR-429低表达的PDAC患者总体生存率和无瘤生存率明显降低（χ2=2.874，3.106；P<0.05）。MTT法检测显示miR-429过表达明显抑制Bxpc-3和Panc-1胰腺癌细胞增殖，抑制miR-429表达则促进细胞增殖。Transwell实验结果显示，miR-429上调明显抑制Bxpc-3和Panc-1细胞的侵袭和迁移能力。免疫荧光染色检测显示，miR-429低表达组织中E-cadherin表达增强，而N-cadherin、vimentin表达降低。

结论

PDAC组织miR-429低表达，低表达与患者生存预后差相关。miR-429通过调控EMT过程在PDAC中发挥抑癌基因作用。

关键词: 胰腺肿瘤, 微RNAs, 肿瘤侵润, 肿瘤转移
Objective

To evaluate the prognostic value and mechanism of miR-429 in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

Clinicopathological data of 95 PDAC patients admitted to Xuyi People's Hospital of Jiangsu province from June 2015 to August 2019 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 60 patients were male and 35 female, aged from 32 to 76 years, with a median age of 61 years. The expression level of miR-429 was detected by fluorescent quantitative RT-PCR. The relationship between miR-429 expression and survival and prognosis of the patients was analyzed. Human pancreatic cancer cell lines Bxpc-3 and Panc-1 were selected for cell experiment. The cell proliferation and migration capability was determined by MTT assay and Transwell chamber test. The expression levels of E-cadherin, N-cadherin and vimentin related to epithelial-mesenchymal transition (EMT) were detected by immunofluorescent staining. The relative expression level of miR-429 between two groups was compared by t test. The relationship between miR-429 expression and clinicopathological features of PDAC patients was analyzed by Chi-square test. Survival analysis was performed with Kaplan-Meier method and Log-rank test.

Results

The average relative expression level of miR-429 in tumor tissues of PDAC patients was 1.02±0.43, significantly lower than 2.35±0.27 in the adjacent normal tissues (t=-1.732, P<0.05). The expression level of miR-429 was correlated with TNM staging and tumor vascular invasion (χ2=3.877, 2.584; P<0.05). The overall survival and disease-free survival rates of PDAC patients with low expression of miR-429 were significantly decreased (χ2=2.874, 3.106; P<0.05). MTT assay revealed that miR-429 overexpression significantly inhibited the proliferation of Bxpc-3 and Panc-1 pancreatic cancer cells, whereas down-regulating miR-429 expression promoted cell proliferation. Up-regulation of miR-429 expression significantly inhibited the invasion and migration of Bxpc-3 and Panc-1 cells according to Transwell chamber test. The expression level of E-cadherin was up-regulated, whereas those of N-cadherin and vimentin were down-regulated in the tissues with low expression of miR-429 according to immunofluorescent staining.

Conclusions

miR-429 is lowly expressed in the PDAC tissues, which is associated with poor prognosis. miR-429 plays an anti-tumor role in PDAC patients by regulating the EMT process.

Key words: Pancreatic neoplasms, MicroRNAs, Neoplasm invasiveness, Neoplasm metastasis
图1 胰腺导管腺癌患者Kaplan-Meier生存曲线
图2 miR-429对Bxpc-3和Panc-1胰腺癌细胞增殖的作用曲线注：示miR-429过表达显著抑制胰腺癌细胞增殖；NC为对照组
图3 细胞克隆形成实验检测miR-429对Bxpc-3胰腺癌细胞增殖的作用注：miR-429类似物抑制细胞克隆形成，其抑制物促进细胞克隆形成；NC为对照组
图4 Transwell实验检测miR-429在Bxpc-3胰腺癌细胞迁移中的作用注：miR-429类似物可抑制细胞迁移，而其抑制物促进细胞迁移；NC为对照组，*为P<0.05
图5 免疫荧光染色检测miR-429与EMT相关因子的关系注：miR-429低表达与E-cadherin高表达和vimentin低表达相关，而miR-429过表达可导致E-cadherin表达降低和vimentin表达上调；EMT为上皮-间质转化，NC为对照组
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