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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation

Authors: Jun Yu, Kenoki Ohuchida, Kazuhiro Mizumoto, Norihiro Sato, Tadashi Kayashima, Hayato Fujita, Kouhei Nakata, Masao Tanaka

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Recently, the microRNA-200 family was reported to affect cancer biology by regulating epithelial to mesenchymal transition (EMT). Especially, the expression of miR-200c has been shown to be associated with upregulating the expression of E-cadherin, a gene known to be involved in pancreatic cancer behavior. However, the significance of miR-200c in pancreatic cancer is unknown.

Methods

In the present study, we investigated the relationship between E-cadherin and miR-200c expression in a panel of 14 pancreatic cancer cell lines and in macro-dissected formalin-fixed paraffin-embedded (FFPE) tissue samples obtained from 99 patients who underwent pancreatectomy for pancreatic cancer. We also investigated the effects of miR-200c on the proliferation and invasion of pancreatic cancer cells.

Results

We found that patients with high levels of miR-200c expression had significantly better survival rates than those with low levels of miR-200c expression. We also found a remarkably strong correlation between the levels of miR-200c and E-cadherin expression.

Conclusions

These data indicate that miR-200c may play a role in the pancreatic cancer biology and may be a novel marker for the prognosis of pancreatic cancer.
Appendix
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Literature
1.
Matsuno S, Egawa S, Fukuyama S, Motoi F, Sunamura M, Isaji S, Imaizumi T, Okada S, Kato H, Suda K, Nakao A, Hiraoka T, Hosotani R, Takeda K: Pancreatic Cancer Registry in Japan: 20 years of experience. Pancreas. 2004, 28: 219-30. 10.1097/00006676-200404000-00002CrossRefPubMed
2.
Yamamoto M, Ohashi O, Saitoh Y: Japan Pancreatic Cancer Registry: current status. Pancreas. 1998, 16: 238-42. 10.1097/00006676-199804000-00006CrossRefPubMed
3.
Habbe N, Koorstra JB, Mendell JT, Offerhaus GJ, Ryu JK, Feldmann G, Mullendore ME, Goggins MG, Hong SM, Maitra A: MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol Ther. 2009, 8: 340-6.PubMedCentralCrossRefPubMed
4.
Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988, 53: 549-54. 10.1016/0092-8674(88)90571-5CrossRefPubMed
5.
Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE: Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet. 1994, 8: 27-32. 10.1038/ng0994-27CrossRefPubMed
6.
Tezel E, Hibi K, Nagasaka T, Nakao A: PGP9.5 as a prognostic factor in pancreatic cancer. Clin Cancer Res. 2000, 6: 4764-7.PubMed
7.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-97. 10.1016/S0092-8674(04)00045-5CrossRefPubMed
8.
Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002, 99: 15524-9. 10.1073/pnas.242606799PubMedCentralCrossRefPubMed
9.
Michael MZ, O' Connor SM, van Holst Pellekaan NG, Young GP, James RJ: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003, 1: 882-91.PubMed
10.
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ: RAS is regulated by the let-7 microRNA family. Cell. 2005, 120: 635-47. 10.1016/j.cell.2005.01.014CrossRefPubMed
11.
He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 2005, 435: 828-33. 10.1038/nature03552PubMedCentralCrossRefPubMed
12.
Calin GA, Croce CM: Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. J Clin Invest. 2007, 117: 2059-66. 10.1172/JCI32577PubMedCentralCrossRefPubMed
13.
Wijnhoven BP, Michael MZ, Watson DI: MicroRNAs and cancer. Br J Surg. 2007, 94: 23-30. 10.1002/bjs.5673CrossRefPubMed
14.
Cochrane DR, Howe EN, Spoelstra NS, Richer JK: Loss of miR-200c: A Marker of aggressiveness and chemoresistance in female reproductive cancers. J Oncol. 2010, 2010: 821717-PubMedCentralCrossRefPubMed
15.
Cochrane DR, Spoelstra NS, Howe EN, Nordeen SK, Richer JK: MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther. 2009, 8: 1055-66. 10.1158/1535-7163.MCT-08-1046.PubMedCentralCrossRefPubMed
16.
Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009, 138: 592-603. 10.1016/j.cell.2009.07.011PubMedCentralCrossRefPubMed
17.
Hurteau GJ, Carlson JA, Spivack SD, Brock GJ: Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer Res. 2007, 67: 7972-6. 10.1158/0008-5472.CAN-07-1058CrossRefPubMed
18.
Hurteau GJ, Carlson JA, Roos E, Brock GJ: Stable expression of miR-200c alone is sufficient to regulate TCF8(ZEB1) and restore E-cadherin expression. Cell cycle. 2009, 8: 2064-9.CrossRefPubMed
19.
Park SM, Gaur AB, Lengyel E, Peter ME: The miR-200 family determines the ephthelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008, 22: 894-907. 10.1101/gad.1640608PubMedCentralCrossRefPubMed
20.
Li Y, VandenBoom TG, Kong D, Ali S, Philip PA, Sarkar FH: Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res. 2009, 69: 6704-12. 10.1158/0008-5472.CAN-09-1298PubMedCentralCrossRefPubMed
21.
Wang F, Sloss C, Zhang X, Lee SW, Cusack JC: Membrane-bound heparin-binding epidermal growth factor like growth factor regulates E-cadherin expression in pancreatic carcinoma cells. Cancer Res. 2007, 67: 8486-93. 10.1158/0008-5472.CAN-07-0498CrossRefPubMed
22.
Howard EW, Camm KD, Wong YC, Wang XH: E-cadherin upregulation as a therapeutic goal in cancer treatment. Mini Rev Med Chem. 2008, 8: 496-518. 10.2174/138955708784223521CrossRefPubMed
23.
Kuniyasu H, Ellis LM, Evans DB, Abbruzzese JL, Fenoglio CJ, Bucana CD, Cleary KR, Tahara E, Fidler IJ: Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma. Clin Cancer Res. 1999, 5: 25-33.PubMed
24.
von Burstin J, Eser S, Paul MC, Seidler B, Brandl M, Messer M, von Werder A, Schmidt A, Mages J, Pagel P, Schnieke A, Schmid RM, Schneider G, Saur D: E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology. 2009, 137: 361-71. 10.1053/j.gastro.2009.04.004CrossRefPubMed
25.
Ohuchida K, Mizumoto K, Murakami M, Qian LW, Sato N, Nagai E, Matsumoto K, Nakamura T, Tanaka M: Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res. 2004, 64: 3215-22. 10.1158/0008-5472.CAN-03-2464CrossRefPubMed
26.
Yu J, Ohuchida K, Nakata K, Mizumoto K, Cui L, Fujita H, Yamaguchi H, Egami T, Kitada H, Tanaka M: LIM only 4 is overexpressed in late stage pancreas cancer. Mol Cancer. 2008, 7: 93- 10.1186/1476-4598-7-93PubMedCentralCrossRefPubMed
27.
Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS: Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003, 5: 34-41.PubMedCentralCrossRefPubMed
28.
Godfrey TE, Kim SH, Chavira M, Ruff DW, Warren RS, Gray JW, Jensen RH: Quantitative mRNA expression analysis from formalin-fixed, paraffin-embedded tissues using 5' nuclease quantitative reverse transcription-polymerase chain reaction. J Mol Diagn. 2000, 2: 84-91.PubMedCentralCrossRefPubMed
29.
Ohuchida K, Mizumoto K, Ishikawa N, Fujii K, Konomi H, Nagai E, Yamaguchi K, Tsuneyoshi M, Tanaka M: The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res. 2005, 11: 7785-93. 10.1158/1078-0432.CCR-05-0714CrossRefPubMed
30.
Nieminen AL, Gores GJ, Bond JM, Imberti R, Herman B, Lemasters JJ: A novel cytotoxicity screening assay using a multiwell fluorescence scanner. Toxicol Appl Pharmacol. 1992, 115: 147-55. 10.1016/0041-008X(92)90317-LCrossRefPubMed
31.
Zhang L, Mizumoto K, Sato N, Ogawa T, Kusumoto M, Niiyama H, Tanaka M: Quantitative determination of apoptotic death in cultured human pancreatic cancer cells by propidium iodide and digitonin. Cancer Lett. 1999, 142: 129-37. 10.1016/S0304-3835(99)00107-XCrossRefPubMed
32.
Sato N, Maehara N, Mizumoto K, Nagai E, Yasoshima T, Hirata K, Tanaka M: Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion. Cancer. 2001, 91: 496-504. 10.1002/1097-0142(20010201)91:3<496::AID-CNCR1028>3.0.CO;2-0CrossRefPubMed
33.
Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Höfler H: E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994, 54: 3845-52.PubMed
34.
Vleminckx K, Vakaet L, Mareel M, Fiers W, van Roy F: Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991, 66: 107-19. 10.1016/0092-8674(91)90143-MCrossRefPubMed
35.
36.
Mees ST, Mardin WA, Wendel C, Baeumer N, Willscher E, Senninger N, Schleicher C, Colombo-Benkmann M, Haier J: EP300-a miRNA-regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas. Int J Cancer. 2010, 126: 114-24. 10.1002/ijc.24695CrossRefPubMed
37.
Lollini PL, Bosco MC, Cavallo F, De Giovanni C, Giovarelli M, Landuzzi L, Musiani P, Modesti A, Nicoletti G, Palmieri G: Inhibition of tumor growth and enhancement of metastasis after transfection of the gamma-interferon gene. Int J Cancer. 1993, 55: 320-9. 10.1002/ijc.2910550224CrossRefPubMed
38.
Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Höfler H, Becker KF: The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer. 2008, 98: 489-95. 10.1038/sj.bjc.6604115PubMedCentralCrossRefPubMed
39.
Li J, Smyth P, Flavin R, Cahill S, Denning K, Aherne S, Guenther SM, O'Leary JJ, Sheils O: Comparison of miRNA expression patterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol. 2007, 7: 36- 10.1186/1472-6750-7-36PubMedCentralCrossRefPubMed
40.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008, 105: 10513-8. 10.1073/pnas.0804549105PubMedCentralCrossRefPubMed
Metadata
Title
MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation
Authors
Jun Yu
Kenoki Ohuchida
Kazuhiro Mizumoto
Norihiro Sato
Tadashi Kayashima
Hayato Fujita
Kouhei Nakata
Masao Tanaka
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-169

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