胰腺癌组织中 Beclin-1 mRNA 和 miR-216a 的表达及 VEGF 蛋白表达与 p-MAPK-ERK1/2信号通路的关系_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

胡伟 ,  沈丰 , 张桢 , 吴红伟 , 周文波

湖北医药学院附属东风医院肝胆胰外科（湖北十堰 442000）;

Corresponding author：

沈丰, Email: 3068006@qq.com

Keywords：

胰腺癌; Beclin-1 mRNA; microRNA-216a; 血管内皮生长因子; 磷酸化细胞外调节蛋白激酶 1/2

DOI：

10.7507/1007-9424.201712086

Video：

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目的探讨腺癌、鳞癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺组织中胰腺癌相关基因的表达。方法回顾性收集 2012 年 1 月至 2017 年 4 月期间于湖北医药学院附属东风医院肝胆胰外科住院行手术治疗的 40 例胰腺疾病患者的术中标本，其中腺癌、鳞癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺组织各 8 例。采用实时荧光定量 PCR 和基因芯片法检测 5 组组织中 Beclin-1 mRNA 和 microRNA（miR）-216a 的表达。对以上组织行原代细胞培养，分为空白对照组和 PD98095 组（加入 PD98095 抑制剂），采用 Western blot 法检测细胞中血管内皮生长因子（VEGR）与磷酸化细胞外调节蛋白激酶 1/2（p-ERK1/2）的表达。结果与正常对照组比较，腺癌组和鳞癌组组织中 Beclin-1 mRNA 和 miR-216a 的表达水平较低（P<0.05），腺癌组、鳞癌组、黏液性囊腺瘤组和慢性胰腺炎组组织中 Beclin-1 mRNA 和 miR-216a 的表达水平比较差异无统计学意义（P>0.05）。与同类组织的空白对照组比较，腺癌组和鳞癌组加入 PD98095 后，细胞中 p-ERK1/2 和 VEGF 蛋白的表达水平下调（P<0.05），但黏液性囊腺瘤组、慢性胰腺炎组和正常对照组加入 PD98095 前后细胞中 p-ERK1/2 及 VEGF 蛋白的表达水平变化不大（P>0.05）。结论 Beclin-1 mRNA、miR-216a 和 VEGF 蛋白的表达与胰腺癌的发生发展可能有关。

Citation： 胡伟, 沈丰, 张桢, 吴红伟, 周文波. 胰腺癌组织中 Beclin-1 mRNA 和 miR-216a 的表达及 VEGF 蛋白表达与 p-MAPK-ERK1/2信号通路的关系. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(7): 859-862. doi: 10.7507/1007-9424.201712086 Copy

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6.	Cho SY, Lee HJ, Jeong SJ, et al. Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1α inactivation in hypoxic PC-3 prostate cancer cells. J Pineal Res, 2011, 51(1): 87-93.
7.	Zhang D, Li B, Shi J, et al. Suppression of tumor growth and metastasis by simultaneously blocking vascular endothelial growth factor (VEGF)-A and VEGF-C with a receptor-immunoglobulin fusion protein. Cancer Res, 2010, 70(6): 2495-2503.
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14.	Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene, 2007, 26(30): 4442-4452.
15.	Kong XY, Du YQ, Li L, et al. Plasma miR-216a as a potential marker of pancreatic injury in a rat model of acute pancreatitis. World J Gastroenterol, 2010, 16(36): 4599-4604.
16.	Cui P, Yu M, Peng X, et al. Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression. J Pineal Res, 2012, 52(2): 236-243.
17.	Won KY, Kim GY, Kim YW, et al. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol, 2010, 41(1): 107-112.

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin, 2012, 62(1): 10-29.
2. Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol, 2010, 7(3): 163-172.
3. Long J, Zhang Y, Yu X, et al. Overcoming drug resistance in pancreatic cancer. Expert Opin Ther Targets, 2011, 15(7): 817-828.
4. Duffy MJ, Sturgeon C, Lamerz R, et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol, 2010, 21(3): 441-447.
5. Wan C, Shen Y, Yang T, et al. Diagnostic value of microRNA for pancreatic cancer: a meta-analysis. Arch Med Sci, 2012, 8(5): 749-755.
6. Cho SY, Lee HJ, Jeong SJ, et al. Sphingosine kinase 1 pathway is involved in melatonin-induced HIF-1α inactivation in hypoxic PC-3 prostate cancer cells. J Pineal Res, 2011, 51(1): 87-93.
7. Zhang D, Li B, Shi J, et al. Suppression of tumor growth and metastasis by simultaneously blocking vascular endothelial growth factor (VEGF)-A and VEGF-C with a receptor-immunoglobulin fusion protein. Cancer Res, 2010, 70(6): 2495-2503.
8. Miracco C, Cevenini G, Franchi A, et al. Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions. Hum Pathol, 2010, 41(4): 503-512.
9. Henry JC, Bassi C, Giovinazzo F, et al. MicroRNA from pancreatic duct aspirate differentiates cystic lesions of the pancreas. Ann Surg Oncol, 2013, 20 Suppl 3: S661-S666.
10. Park JK, Henry JC, Jiang J, et al. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor. Biochem Biophys Res Commun, 2011, 406(4): 518-523.
11. Puri A, Saif MW. Pharmacogenomics update in pancreatic cancer. JOP, 2014, 15(2): 114-117.
12. Nagao Y, Hisaoka M, Matsuyama A, et al. Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma. Mod Pathol, 2012, 25(1): 112-121.
13. Yu M, Gou WF, Zhao S, et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas. Tumour Biol, 2013, 34(2): 1071-1083.
14. Szafranska AE, Davison TS, John J, et al. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene, 2007, 26(30): 4442-4452.
15. Kong XY, Du YQ, Li L, et al. Plasma miR-216a as a potential marker of pancreatic injury in a rat model of acute pancreatitis. World J Gastroenterol, 2010, 16(36): 4599-4604.
16. Cui P, Yu M, Peng X, et al. Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression. J Pineal Res, 2012, 52(2): 236-243.
17. Won KY, Kim GY, Kim YW, et al. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol, 2010, 41(1): 107-112.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

胰腺癌组织中 Beclin-1 mRNA 和 miR-216a 的表达及 VEGF 蛋白表达与 p-MAPK-ERK1/2信号通路的关系

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