Cell & Bioscience | |
MicroRNA-206 suppresses gastric cancer cell growth and metastasis | |
Steven Y Cheng1  Li-ming Tang2  Shen Yue1  Yu Gong2  Hui-jie Huang1  Jun Ren1  | |
[1] Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, 210029 Nanjing, Jiangsu, PR. China;Department of General Surgery, Nanjing Medical University affiliated Changzhou No. 2 Hospital, 213000 Changzhou, Jiangsu, PR. China | |
关键词: Tumor suppressor; Metastasis; miR-206; Gastric cancer; | |
Others : 790674 DOI : 10.1186/2045-3701-4-26 |
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received in 2014-02-06, accepted in 2014-03-15, 发布年份 2014 | |
【 摘 要 】
Gastric cancer is one of the leading causes of cancer death world-wide and carries a high rate of metastatic risk. In addition to other protein-coding oncogenes and tumor suppressor genes, microRNAs play an important role in gastric cancer tumorigenic progression. Here, we show that miR-206 is expressed at markedly low levels in a cohort of gastric tumors compared to their matching normal tissues, and in a number of gastric cancer cell lines. Down-regulation of miR-206 was particularly significant in tumors with lymphatic metastasis, local invasion, and advanced TNM staging. We find that forced expression of miR-206 suppressed the proliferation, colony-formation, and xenograft tumorigenesis of SCG-7901 cells, a line of gastric cancer cells. Forced expression of miR-206 also suppressed SCG-7901 cell migration and invasion, as well as metastasis in cell culture or tail-vein injected mouse models, respectively. The anti-metastatic effect of miR-206 is likely mediated by targeting metastasis regulatory genes STC2, HDAC4, KLF4, IGF1R, FRS2, SFRP1, BCL2, BDNF, and K-ras, which were drastically down-regulated by stable expression of exogenous miR-206 in SCG-7901 cells. Taken together, our results indicate that miR-206 is a tumor suppressor of gastric cancer acting at steps that regulate metastasis.
【 授权许可】
2014 Ren et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M: Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 2005, 366:1784-1793.
- [2]Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F, Van Cutsem E: Gastric cancer. Crit Rev Oncol Hematol 2009, 71:127-164.
- [3]Houghton J, Wang TC: Helicobacter pylori and gastric cancer: a new paradigm for inflammation-associated epithelial cancers. Gastroenterology 2005, 128:1567-1578.
- [4]Pounder RE, Ng D: The prevalence of Helicobacter pylori infection in different countries. Aliment Pharmacol Ther 1995, 9(Suppl 2):33-39.
- [5]Coyle WJ, Sedlack RE, Nemec R, Peterson R, Duntemann T, Murphy M, Lawson JM: Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor. Am J Gastroenterol 1999, 94:2885-2889.
- [6]Chan AO, Peng JZ, Lam SK, Lai KC, Yuen MF, Cheung HK, Kwong YL, Rashid A, Chan CK, Wong BC: Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation. Gut 2006, 55:463-468.
- [7]Ren G, Tian Q, An Y, Feng B, Lu Y, Liang J, Li K, Shang Y, Nie Y, Wang X, Fan D: Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K. Mol Cancer 2007, 11:67.
- [8]Kubben FJ, Sier CF, Schram MT, Witte AM, Veenendaal RA, van Duijn W, Verheijen JH, Hanemaaijer R, Lamers CB, Verspaget HW: Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels. Helicobacter 2007, 12:498-504.
- [9]Ushijima T, Sasako M: Focus on gastric cancer. Cancer Cell 2004, 5:121-125.
- [10]Yokobori T, Mimori K, Ishii H, Iwatsuki M, Tanaka F, Kamohara Y, Ieta K, Kita Y, Doki Y, Kuwano H, Mori M: Clinical significance of stanniocalcin 2 as a prognostic marker in gastric cancer. Ann Surg Oncol 2010, 17:2601-2607.
- [11]Arigami T, Uenosono Y, Ishigami S, Yanagita S, Hagihara T, Haraguchi N, Matsushita D, Hirahara T, Okumura H, Uchikado Y, Nakajo A, Hokita S, Natsugoe S: Clinical significance of stanniocalcin 2 expression as a predictor of tumor progression in gastric cancer. Oncol Rep 2013, 30:2838-2844.
- [12]Okugawa Y, Tanaka K, Inoue Y, Kawamura M, Kawamoto A, Hiro J, Saigusa S, Toiyama Y, Ohi M, Uchida K, Mohri Y, Kusunoki M: Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer. Br J Cancer 2013, 108:121-130.
- [13]Townley-Tilson WH, Callis TE, Wang D: MicroRNAs 1, 133, and 206: critical factors of skeletal and cardiac muscle development, function, and disease. Int J Biochem Cell Biol 2010, 42:1252-1255.
- [14]Nohata N, Hanazawa T, Enokida H, Seki N: microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget 2012, 3:9-21.
- [15]Yoshino H, Chiyomaru T, Enokida H, Kawakami K, Tatarano S, Nishiyama K, Nohata N, Seki N, Nakagawa M: The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer. Br J Cancer 2011, 104:808-818.
- [16]Yan D, Dong Xda E, Chen X, Wang L, Lu C, Wang J, Qu J, Tu L: MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development. J Biol Chem 2009, 284:29596-29604.
- [17]O'Day E, Lal A: MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res 2010, 12:201. BioMed Central Full Text
- [18]Wang X, Ling C, Bai Y, Zhao J: MicroRNA-206 is associated with invasion and metastasis of lung cancer. Anat Rec (Hoboken) 2011, 294:88-92.
- [19]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR: MicroRNA expression profiles classify human cancers. Nature 2005, 435:834-838.
- [20]Kita Y, Mimori K, Iwatsuki M, Yokobori T, Ieta K, Tanaka F, Ishii H, Okumura H, Natsugoe S, Mori M: STC2: a predictive marker for lymph node metastasis in esophageal squamous-cell carcinoma. Ann Surg Oncol 2011, 18:261-272.
- [21]Okamura K, Harada T, Wang S, Ijichi K, Furuyama K, Koga T, Okamoto T, Takayama K, Yano T, Nakanishi Y: Expression of TrkB and BDNF is associated with poor prognosis in non-small cell lung cancer. Lung Cancer 2012, 78:100-106.
- [22]Hellawell GO, Ferguson DJ, Brewster SF, Macaulay VM: Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. BJU Int 2003, 91:271-277.
- [23]Krueckl SL, Sikes RA, Edlund NM, Bell RH, Hurtado-Coll A, Fazli L, Gleave ME, Cox ME: Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model. Cancer Res 2004, 64:8620-8629.
- [24]Fleischmann A, Huland H, Mirlacher M, Wilczak W, Simon R, Erbersdobler A, Sauter G, Schlomm T: Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene. Prostate 2012, 72:991-997.
- [25]Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H: miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 2008, 68:5004-5008.
- [26]Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, Ladanyi M, Tuschl T, Ponzetto C: The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J Clin Invest 2009, 119:2366-2378.
- [27]Song G, Zhang Y, Wang L: MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation. J Biol Chem 2009, 284:31921-31927.
- [28]Chen X, Yan Q, Li S, Zhou L, Yang H, Yang Y, Liu X, Wan X: Expression of the tumor suppressor miR-206 is associated with cellular proliferative inhibition and impairs invasion in ERalpha-positive endometrioid adenocarcinoma. Cancer Lett 2012, 314:41-53.
- [29]Leong T: Chemotherapy and radiotherapy in the management of gastric cancer. Curr Opin Gastroenterol 2005, 21:673-678.
- [30]Jiang Y, Wang L, Gong W, Wei D, Le X, Yao J, Ajani J, Abbruzzese JL, Huang S, Xie K: A high expression level of insulin-like growth factor I receptor is associated with increased expression of transcription factor Sp1 and regional lymph node metastasis of human gastric cancer. Clin Exp Metastasis 2004, 21:755-764.
- [31]Zhao X, Dou W, He L, Liang S, Tie J, Liu C, Li T, Lu Y, Mo P, Shi Y, Wu K, Nie Y, Fan D: MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor. Oncogene 2013, 32:1363-1372.
- [32]Adachi Y, Li R, Yamamoto H, Min Y, Piao W, Wang Y, msumran A, Li H, Arimura Y, Lee CT, Imai K, Carbone DP, Shinomura Y: Insulin-like growth factor-I receptor blockade reduces the invasiveness of gastrointestinal cancers via blocking production of matrilysin. Carcinogenesis 2009, 30:1305-1313.
- [33]Terracciano LM, Glatz K, Mhawech P, Vasei M, Lehmann FS, Vecchione R, Tornillo L: Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases. Am J Surg Pathol 2003, 27:1302-1312.
- [34]Cheon SH, Rha SY, Jeung HC, Im CK, Kim SH, Kim HR, Ahn JB, Roh JK, Noh SH, Chung HC: Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases. Ann Oncol 2008, 19:1146-1153.