期刊论文详细信息
Journal of Experimental & Clinical Cancer Research
miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1
Kaixing Ai1  Zhou Yuan1  Xinyu Huang1  Weiwei Wang1  Hongda Zhu1  Yueqing Bai2  Bo Dong1  Bo Wu1  Kate Nong1  Chenchao Ma1 
[1] Department of General Surgery, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China;Department of Pathology, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China
关键词: Invasion;    Migration;    Proliferation;    Pancreatic cancer;    Patched-1;    miR-212;   
Others  :  824009
DOI  :  10.1186/1756-9966-33-54
 received in 2014-04-16, accepted in 2014-06-20,  发布年份 2014
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【 摘 要 】

Background

microRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in carcinogenesis. In the present study, we investigated the effect of miR-212 on pancreatic ductal adenocarcinoma (PDAC) and its target protein.

Methods

Quantitative real-time PCR(qRT-PCR) was performed to detect the expression of miR-212 in PDAC tissues and pancreatic cancer cell lines. miR-212 mimic, miR-212 inhibitor and negative control were transfected into pancreatic cancer cells and the effect of miR-212 up-regulation and down-regulation on the proliferation, migration and invasion of cells were investigated. Furthermore, the mRNA and protein levels of Patched-1(PTCH1) were measured. Meanwhile, luciferase assays were performed to validate PTCH1 as miR-212 target in PDAC.

Results

miR-212 was up-regulated in PDAC tissues and cells.Using both gain-of function and loss-of function experiments, a pro-oncogenic function of miR-212 was demonstrated in PDAC. Moreover, up-regulated of PTCH1 could attenuate the effect induced by miR-212.

Conclusion

These data suggest that miR-212 could facilitate PDAC progression and metastasis through targeting PTCH1, implicating a novel mechanism for the progression of PDAC.

【 授权许可】

   
2014 Ma et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Guled M, Knuutila S: MicroRNAs and cancer. Duodecim 2013, 129(16):1661-1669.
  • [2]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116(2):281-297.
  • [3]Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009, 136(2):215-233.
  • [4]Shenouda SK, Alahari SK: MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 2009, 28(3–4):369-378.
  • [5]Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer 2006, 6(11):857-866.
  • [6]Ma L, Weinberg RA: Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet 2008, 24(9):448-456.
  • [7]Bouyssou JM, Manier S, Huynh D, Issa S, Roccaro AM, Ghobrial IM: Regulation of microRNAs in cancer metastasis. Biochim Biophys Acta 2014, 1845(2):255-265.
  • [8]Bracken CP, Gregory PA, Khew-Goodall Y, Goodall GJ: The role of microRNAs in metastasis and epithelial-mesenchymal transition. Cell Mol Life Sci 2009, 66(10):1682-1699.
  • [9]Ma MZ, Kong X, Weng MZ, Cheng K, Gong W, Quan ZW, Peng CH: Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance. J Exp Clin Cancer Res 2013, 32(1):71.
  • [10]Guan P, Yin Z, Li X, Wu W, Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res 2012, 31:54.
  • [11]Wang C, Zheng X, Shen C, Shi Y: MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. J Exp Clin Cancer Res 2012, 31:58.
  • [12]Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA: MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer 2009, 9(4):293-302.
  • [13]Li Y, Zhang D, Chen C, Ruan Z, Li Y, Huang Y: MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1. Mol Biol Cell 2012, 23(8):1423-1434.
  • [14]Scapoli L, Palmieri A, Lo ML, Pezzetti F, Rubini C, Girardi A, Farinella F, Mazzotta M, Carinci F: MicroRNA expression profiling of oral carcinoma identifies new markers of tumor progression. Int J Immunopathol Pharmacol 2010, 23(4):1229-1234.
  • [15]Liang X, Zeng J, Wang L, Fang M, Wang Q, Zhao M, Xu X, Liu Z, Li W, Liu S, Yu H, Jia J, Chen C: Histone demethylase retinoblastoma binding protein 2 is overexpressed in hepatocellular carcinoma and negatively regulated by hsa-miR-212. PLoS ONE 2013, 8(7):e69784.
  • [16]Jiping Z, Ming F, Lixiang W, Xiuming L, Yuqun S, Han Y, Zhifang L, Yundong S, Shili L, Chunyan C, Jihui J: MicroRNA-212 inhibits proliferation of gastric cancer by directly repressing retinoblastoma binding protein 2. J Cell Biochem 2013, 114(12):2666-2672.
  • [17]Xu L, Wang F, Xu XF, Mo WH, Xia YJ, Wan R, Wang XP, Guo CY: Down-regulation of miR-212 expression by DNA hypermethylation in human gastric cancer cells. Med Oncol 2011, 28(Suppl 1):S189-S196.
  • [18]Meng X, Wu J, Pan C, Wang H, Ying X, Zhou Y, Yu H, Zuo Y, Pan Z, Liu RY, Huang W: Genetic and epigenetic down-regulation of microRNA-212 promotes colorectal tumor metastasis via dysregulation of MnSOD. Gastroenterology 2013, 145(2):426-436.
  • [19]Walter BA, Valera VA, Pinto PA, Merino MJ: Comprehensive microRNA profiling of prostate cancer. J Cancer 2013, 4(5):350-357.
  • [20]Yamaguchi H, Kojima T, Ito T, Kimura Y, Imamura M, Son S, Koizumi J, Murata M, Nagayama M, Nobuoka T, Tanaka S, Hirata K, Sawada N: Transcriptional control of tight junction proteins via a protein kinase C signal pathway in human telomerase reverse transcriptase-transfected human pancreatic duct epithelial cells. Am J Pathol 2010, 177(2):698-712.
  • [21]Osada H, Takahashi T: MicroRNAs in biological processes and carcinogenesis. Carcinogenesis 2007, 28(1):2-12.
  • [22]Park JK, Henry JC, Jiang J, Esau C, Gusev Y, Lerner MR, Postier RG, Brackett DJ, Schmittgen TD: 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.
  • [23]Stone DM, Hynes M, Armanini M, Swanson TA, Gu Q, Johnson RL, Scott MP, Pennica D, Goddard A, Phillips H, Noll M, Hooper JE, de Sauvage F, Rosenthal A: The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog. Nature 1996, 384(6605):129-134.
  • [24]Thayer SP, di Magliano MP, Heiser PW, Nielsen CM, Roberts DJ, Lauwers GY, Qi YP, Gysin S, Fernandez-del CC, Yajnik V, Antoniu B, McMahon M, Warshaw AL, Hebrok M: Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 2003, 425(6960):851-856.
  • [25]Jiang J, Hui CC: Hedgehog signaling in development and cancer. Dev Cell 2008, 15(6):801-812.
  • [26]Gao J, Li Z, Chen Z, Shao J, Zhang L, Xu G, Tu Z, Gong Y: Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer. Gene Ther 2006, 13(22):1587-1594.
  • [27]Fu X, Wang Q, Chen X, Huang X, Cao L, Tan H, Li W, Zhang L, Bi J, Su Q, Chen L: Expression patterns and polymorphisms of PTCH in Chinese hepatocellular carcinoma patients. Exp Mol Pathol 2008, 84(3):195-199.
  • [28]Ishiyama A, Hibi K, Koike M, Fujiwara M, Kodera Y, Ito K, Nakao A: PTCH gene expression as a potential marker for esophageal squamous cell carcinoma. Anticancer Res 2006, 26(1A):195-198.
  • [29]Wolf I, Bose S, Desmond JC, Lin BT, Williamson EA, Karlan BY, Koeffler HP: Unmasking of epigenetically silenced genes reveals DNA promoter methylation and reduced expression of PTCH in breast cancer. Breast Cancer Res Treat 2007, 105(2):139-155.
  • [30]You S, Zhou J, Chen S, Zhou P, Lv J, Han X, Sun Y: PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer. Ups J Med Sci 2010, 115(3):169-175.
  • [31]Sheng T, Li C, Zhang X, Chi S, He N, Chen K, McCormick F, Gatalica Z, Xie J: Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer 2004, 3:29.
  • [32]Chi S, Huang S, Li C, Zhang X, He N, Bhutani MS, Jones D, Castro CY, Logrono R, Haque A, Zwischenberger J, Tyring SK, Zhang H, Xie J: Activation of the hedgehog pathway in a subset of lung cancers. Cancer Lett 2006, 244(1):53-60.
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