胰腺癌組織中 Beclin-1 mRNA 和 miR-216a 的表達及 VEGF 蛋白表達與 p-MAPK-ERK1/2信號通路的關系_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

胡偉 ,  沈豐 , 張楨 , 吳紅偉 , 周文波

湖北醫藥學院附屬東風醫院肝膽胰外科（湖北十堰 442000）;

Corresponding?author：

沈豐, Email: 3068006@qq.com

Keywords：

胰腺癌; Beclin-1 mRNA; microRNA-216a; 血管內皮生長因子; 磷酸化細胞外調節蛋白激酶 1/2

DOI：

10.7507/1007-9424.201712086

Video：

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目的探討腺癌、鱗癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺組織中胰腺癌相關基因的表達。方法回顧性收集 2012 年 1 月至 2017 年 4 月期間于湖北醫藥學院附屬東風醫院肝膽胰外科住院行手術治療的 40 例胰腺疾病患者的術中標本，其中腺癌、鱗癌、黏液性囊腺瘤、慢性胰腺炎和正常胰腺組織各 8 例。采用實時熒光定量 PCR 和基因芯片法檢測 5 組組織中 Beclin-1 mRNA 和 microRNA（miR）-216a 的表達。對以上組織行原代細胞培養，分為空白對照組和 PD98095 組（加入 PD98095 抑制劑），采用 Western blot 法檢測細胞中血管內皮生長因子（VEGR）與磷酸化細胞外調節蛋白激酶 1/2（p-ERK1/2）的表達。結果與正常對照組比較，腺癌組和鱗癌組組織中 Beclin-1 mRNA 和 miR-216a 的表達水平較低（P<0.05），腺癌組、鱗癌組、黏液性囊腺瘤組和慢性胰腺炎組組織中 Beclin-1 mRNA 和 miR-216a 的表達水平比較差異無統計學意義（P>0.05）。與同類組織的空白對照組比較，腺癌組和鱗癌組加入 PD98095 后，細胞中 p-ERK1/2 和 VEGF 蛋白的表達水平下調（P<0.05），但黏液性囊腺瘤組、慢性胰腺炎組和正常對照組加入 PD98095 前后細胞中 p-ERK1/2 及 VEGF 蛋白的表達水平變化不大（P>0.05）。結論 Beclin-1 mRNA、miR-216a 和 VEGF 蛋白的表達與胰腺癌的發生發展可能有關。

Citation： 胡偉, 沈豐, 張楨, 吳紅偉, 周文波. 胰腺癌組織中 Beclin-1 mRNA 和 miR-216a 的表達及 VEGF 蛋白表達與 p-MAPK-ERK1/2信號通路的關系. 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.
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.
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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.
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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.

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

胰腺癌組織中 Beclin-1 mRNA 和 miR-216a 的表達及 VEGF 蛋白表達與 p-MAPK-ERK1/2信號通路的關系

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