The expressions of microRNA-196b, microRNA-217, and TGFβR1 protein in the pancreatic ductal adenocarcinoma tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MIAO Chunmu , GONG Jianping , XIONG Bin , YOU Ke ,  DENG Kai

Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;

Corresponding author：

DENG Kai, Email: dengk1973@163.com

Keywords：

pancreatic ductal adenocarcinoma; microRNA-196b; microRNA-217; transforming growth factor β receptor 1

DOI：

10.7507/1007-9424.201802009

Video：

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Objective To determine the expression levels of micro RNA (miR)-196, miR-217, and transforming growth factor β receptor 1 (TGFβR1) protein in the pancreatic ductal adenocarcinoma tissues and its adjacent tissues, to reveal the relationship among them in the pathological process of pancreatic ductal adenocarcinoma. Methods A total of 30 cases’ pancreatic ductal adenocarcinoma tissues and its adjacent tissues were collected. The expression levels of miR-196b and miR-217 in the pancreatic ductal adenocarcinoma and adjacent tissues were detected by real-time fluorescence quantitative polymerase chain reaction method, the level of TGFβR1 protein was detected by Western blotting method. Results In the pancreatic ductal adenocarcinoma tissues, the expression levels of miR-196b and TGFβR1 protein were significantly higher than those of adjacent tissues (P<0.001), while the level of miR-217 was significantly lower than that of adjacent tissues (P=0.001). For further detection, the level of miR-196b in pancreatic ductal adenocarcinoma tissues was significantly positively correlated with the expression level of TGFβR1 protein (r=0.803, P<0.001), while the expression level of miR-217 was negatively correlated with the expression level of TGFβR1 protein (r=–0.839, P<0.001). Conclusions Expression TGFβR1 protein in pancreatic ductal adenocarcinoma tissues may be bi-directionally regulated by miR-196b and miR-217. This two-way regulating mechanism may be one of the important mechanisms for restricting the development of pancreatic ductal adenocarcinoma, implying a potential target for treatment of pancreatic cancer.

Citation： MIAO Chunmu, GONG Jianping, XIONG Bin, YOU Ke, DENG Kai. The expressions of microRNA-196b, microRNA-217, and TGFβR1 protein in the pancreatic ductal adenocarcinoma tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(9): 1077-1082. doi: 10.7507/1007-9424.201802009 Copy

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9.	Kanno S, Nosho K, Ishigami K, et al. MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer. Carcinogenesis, 2017, 38(4): 425-431.
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17.	Negoi I, Hostiuc S, Sartelli M, et al. MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer-a systematic review and meta-analysis. Am J Surg, 2017, 214(3): 515-524.
18.	Li CH, Xiao Z, Tong JH, et al. EZH2 coupled with HOTAIR to silence MicroRNA-34a by the induction of heterochromatin formation in human pancreatic ductal adenocarcinoma. Int J Cancer, 2017, 140(1): 120-129.
19.	Yi JM, Kang EJ, Kwon HM, et al. Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer. Oncotarget, 2017, 8(16): 26600-26612.
20.	Liu S, Chen S, Zeng J. TGF-β signaling: a complex role in tumorigenesis (review). Mol Med Rep, 2018, 17(1): 699-704.
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22.	Hu Q, Hisamatsu T, Haemmerle M, et al. Role of platelet-derived Tgfβ1 in the progression of ovarian cancer. Clin Cancer Res, 2017, 23(18): 5611-5621.
23.	Craven KE, Gore J, Wilson JL, et al. Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes. Oncotarget, 2016, 7(1): 323-341.
24.	Principe DR, Diaz AM, Torres C, et al. TGFβ engages MEK/ERK to differentially regulate benign and malignant pancreas cell function. Oncogene, 2017, 36(30): 4336-4348.
25.	Xu X, Chen R, Li Z, et al. MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1. BMC Cancer, 2015, 15: 1023.

1. Thomas H. Pancreatic cancer: intra-tumour bacteria promote gemcitabine resistance in pancreatic adenocarcinoma. Nat Rev Gastroenterol Hepatol, 2017, 14(11): 632.
2. Chin V, Nagrial A, Sjoquist K, et al. Chemotherapy and radiotherapy for advanced pancreatic cancer. Cochrane Database Syst Rev, 2018, 3: CD011044.
3. Vienot A, Beinse G, Louvet C, et al. Overall survival prediction and usefulness of second-line chemotherapy in advanced pancreatic adenocarcinoma. J Natl Cancer Inst, 2017, 109(10): 10.
4. Udumyan R, Montgomery S, Fang F, et al. Beta-blocker drug use and survival among patients with pancreatic adenocarcinoma. Cancer Res, 2017, 77(13): 3700-3707.
5. Treiber T, Treiber N, Plessmann U, et al. A compendium of RNA-binding proteins that regulate microRNA biogenesis. Mol Cell, 2017, 66(2): 270-284.
6. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol, 2018, 141(4): 1202-1207.
7. López-González MJ, Landry M, Favereaux A. MicroRNA and chronic pain: from mechanisms to therapeutic potential. Pharmacol Ther, 2017, 180: 1-15.
8. Rapado-González Ó, Majem B, Muinelo-Romay L, et al. Human salivary microRNAs in cancer. J Cancer, 2018, 9(4): 638-649.
9. Kanno S, Nosho K, Ishigami K, et al. MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer. Carcinogenesis, 2017, 38(4): 425-431.
10. Idichi T, Seki N, Kurahara H, et al. Regulation of actin-binding protein ANLN by antitumor. Oncotarget, 2017, 8(32): 53180-53193.
11. Xia H, Ooi LL, Hui KM. MicroRNA-216a/217-induced epithelial-mesenchymal transition targets PTEN and SMAD7 to promote drug resistance and recurrence of liver cancer. Hepatology, 2013, 58(2): 629-641.
12. Xue Y, Ouyang K, Huang J, et al. Direct conversion of fibroblasts to neurons by reprogramming PTB-regulated microRNA circuits. Cell, 2013, 152(1-2): 82-96.
13. Liu L, Aleksandrowicz E, Schönsiegel F, et al. Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFβ and JNK/AP-1. Cell Death Dis, 2017, 8(10): e3064.
14. Huang PH, Lu PJ, Ding LY, et al. TGFβ promotes mesenchymal phenotype of pancreatic cancer cells, in part, through epigenetic activation of VAV1. Oncogene, 2017, 36(16): 2202-2214.
15. 杨尹默, 刘子文, 赵玉沛, 等. 胰腺癌诊治指南 (2014). 中国实用外科杂志, 2014, 34(11): 1011-1017.
16. Wald P, Liu XS, Pettit C, et al. Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a review of the literature. Oncotarget, 2017, 8(42): 73345-73361.
17. Negoi I, Hostiuc S, Sartelli M, et al. MicroRNA-21 as a prognostic biomarker in patients with pancreatic cancer-a systematic review and meta-analysis. Am J Surg, 2017, 214(3): 515-524.
18. Li CH, Xiao Z, Tong JH, et al. EZH2 coupled with HOTAIR to silence MicroRNA-34a by the induction of heterochromatin formation in human pancreatic ductal adenocarcinoma. Int J Cancer, 2017, 140(1): 120-129.
19. Yi JM, Kang EJ, Kwon HM, et al. Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer. Oncotarget, 2017, 8(16): 26600-26612.
20. Liu S, Chen S, Zeng J. TGF-β signaling: a complex role in tumorigenesis (review). Mol Med Rep, 2018, 17(1): 699-704.
21. Zhao Y, Qiao W, Wang X, et al. 14-3-3ζ/TGFβR1 promotes tumor metastasis in lung squamous cell carcinoma. Oncotarget, 2016, 7(50): 82972-82984.
22. Hu Q, Hisamatsu T, Haemmerle M, et al. Role of platelet-derived Tgfβ1 in the progression of ovarian cancer. Clin Cancer Res, 2017, 23(18): 5611-5621.
23. Craven KE, Gore J, Wilson JL, et al. Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes. Oncotarget, 2016, 7(1): 323-341.
24. Principe DR, Diaz AM, Torres C, et al. TGFβ engages MEK/ERK to differentially regulate benign and malignant pancreas cell function. Oncogene, 2017, 36(30): 4336-4348.
25. Xu X, Chen R, Li Z, et al. MicroRNA-490-3p inhibits colorectal cancer metastasis by targeting TGFβR1. BMC Cancer, 2015, 15: 1023.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expressions of microRNA-196b, microRNA-217, and TGFβR1 protein in the pancreatic ductal adenocarcinoma tissues

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