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01-05-2012 | 2011 SSAT Plenary Presentation

Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma

Authors: Dung-Tsa Chen, Jonathan M. Hernandez, David Shibata, Susan M. McCarthy, Leigh Ann Humphries, Whalen Clark, Abul Elahi, Mike Gruidl, Domenico Coppola, Timothy Yeatman

Published in: Journal of Gastrointestinal Surgery | Issue 5/2012

Abstract

Background

Altered expression of specific microRNAs (miRNA) is known to occur during colorectal carcinogenesis. However, little is known about the genome-wide alterations in miRNA expression during the neoplastic progression of primary colorectal cancers.

Methods

Using a miRNA array platform, we evaluated the expression of 668 miRNA in primary colonic adenocarcinomas. Biological functions of selected miRNA were evaluated with in vitro invasion assays.

Results

RNA was extracted for miRNA analysis from 65 primary colon cancers. We identified a seven-miRNA expression signature that differentiated stage I and stage IV primary colon cancers. We then demonstrated this signature was able to discriminate between stage II and III primary colon cancers. Six differentially expressed miRNA were downregulated in association with the development of metastases, and all 7 miRNA were complementary strand miRNA. We transfected HCT-116, a highly invasive colon cancer cell line, with corresponding downregulated miRNA and demonstrated that overexpression of three miRNA (miR200c*, miR143*, and miR424*) significantly abrogated invasive potential.

Conclusion

We have identified a seven-miRNA signature that is associated with metastatic potential in the primary tumor. Forced overexpression of three downregulated miRNA resulted in attenuation of in vitro invasion, suggesting direct tumor suppressive function and further supporting the biological importance of complementary strand miRNA.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin2010 Sep–Oct;60(5):277–300.PubMedCrossRef

Glud M, Rossing M, Hother C, Holst L, Hastrup N, Nielsen FC, Gniadecki R, Drzewiecki KT. Downregulation of miR-125b in metastatic cutaneous malignant melanoma. Melanoma Res 2010 Dec;20(6):479–84.PubMedCrossRef

Huynh C, Segura MF, Gaziel A, Menendez S, Darvishian F, Chiriboga L, Levine B, Meruelo D, Zavadil J, Marcusson EG, Hernando E. Efficient in vivo miRNA targeting of liver metastasis. Oncogene 2011 Mar 24;30(12):1481–8.

Li Y, Zhang M, Chen H, Dong Z, Ganapathy V, Thangaraju M, Huang S. Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer Res2010 Oct 15;70(20):7894–904.PubMedCrossRef

Roth C, Rack B, Muller V, Janni W, Pantel K, Schwarzenbach H. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res2010 Nov 3;12(6):R90.PubMedCrossRef

Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature2010 Oct 21;467(7318):986–90.PubMedCrossRef

Faber C, Kirchner T, Hlubek F. The impact of microRNAs on colorectal cancer. Virchows Arch2009 Apr;454(4):359–67.PubMedCrossRef

Czech B, Zhou R, Erlich Y, Brennecke J, Binari R, Villalta C, Gordon A, Perrimon N, Hannon GJ. Hierarchical rules for Argonaute loading in Drosophila. Mol Cell2009 Nov 13;36(3):445–56.PubMedCrossRef

Ghildiyal M, Xu J, Seitz H, Weng Z, Zamore PD. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA2010 Jan;16(1):43–56.PubMedCrossRef

10.

Okamura K, Liu N, Lai EC. Distinct mechanisms for microRNA strand selection by Drosophila Argonautes. Mol Cell2009 Nov 13;36(3):431–44.PubMedCrossRef

11.

Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, Kornmann M. Prognostic values of microRNAs in colorectal cancer. Biomark Insights2006;2:113–21.PubMed

12.

Burk U, Schubert J, Wellner U, Schmalhofer O, Vincan E, Spaderna S, Brabletz T. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep2008 Jun;9(6):582–9.PubMedCrossRef

13.

Tibshirani R, Hastie T, Narasimhan B, Chu G. Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A2002 May 14;99(10):6567–72.PubMedCrossRef

14.

Chen DT, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R, Wang T, Agrawal D, McCarthy SM, Gruidl M, Bloom G, Anderson T, White J, Quackenbush J, Yeatman T. Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treat2010 Jan;119(2):335–46.PubMedCrossRef

15.

Baffa R, Fassan M, Volinia S, O'Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol2009 Oct;219(2):214–21.PubMedCrossRef

16.

Budhu A, Jia HL, Forgues M, Liu CG, Goldstein D, Lam A, Zanetti KA, Ye QH, Qin LX, Croce CM, Tang ZY, Wang XW. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology2008 Mar;47(3):897–907.PubMedCrossRef

17.

Iorio MV, Croce CM. MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol2009 Dec 1;27(34):5848–56.PubMedCrossRef

18.

Lujambio A, Calin GA, Villanueva A, Ropero S, Sanchez-Cespedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A2008 Sep 9;105(36):13556–61.PubMedCrossRef

19.

Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szasz AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell2009 Jun 12;137(6):1032–46.PubMedCrossRef

20.

Tsang WP, Kwok TT. The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras. Carcinogenesis2009 Jun;30(6):953–9.PubMedCrossRef

21.

Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, Choung S, Kim YJ, Choi YC. MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem2008 Jun 27;283(26):18158–66.PubMedCrossRef

22.

Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell2007 Dec 14;131(6):1097–108.PubMedCrossRef

23.

Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell2001 Jul 13;106(1):23–34.PubMedCrossRef

24.

Khan AA, Betel D, Miller ML, Sander C, Leslie CS, Marks DS. Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs. Nat Biotechnol2009 Jun;27(6):549–55.PubMed

25.

O'Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, Enright AJ, Miska EA, Tarakhovsky A. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev2007 Aug 15;21(16):1999–2004.PubMedCrossRef

26.

Vaucheret H, Vazquez F, Crete P, Bartel DP. The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes Dev2004 May 15;18(10):1187–97.PubMedCrossRef

27.

Ceppi P, Mudduluru G, Kumarswamy R, Rapa I, Scagliotti GV, Papotti M, Allgayer H. Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer. Mol Cancer Res2010 Sep;8(9):1207–16.PubMedCrossRef

28.

Elson-Schwab I, Lorentzen A, Marshall CJ. MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion. PLoS One2010;5(10).

29.

Hamano R, Miyata H, Yamasaki M, Kurokawa Y, Hara J, Ho Moon J, Nakajima K, Takiguchi S, Fujiwara Y, Mori M, Doki Y. Overexpression of miR-200c induces chemoresistance in esophageal cancers mediated through activation of the akt signaling pathway. Clin Cancer Res2011 Apr 19.

30.

Neves R, Scheel C, Weinhold S, Honisch E, Iwaniuk KM, Trompeter HI, Niederacher D, Wernet P, Santourlidis S, Uhrberg M. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. BMC Res Notes2010;3:219.PubMedCrossRef

31.

Smith CM, Watson DI, Leong MP, Mayne GC, Michael MZ, Wijnhoven BP, Hussey DJ. miR-200 Family expression is downregulated upon neoplastic progression of Barrett's esophagus. World J Gastroenterol2011 Feb 28;17(8):1036–44.PubMed

32.

Yu J, Ohuchida K, Mizumoto K, Sato N, Kayashima T, Fujita H, Nakata K, Tanaka M. MicroRNA, hsa-miR-200c, is an independent prognostic factor in pancreatic cancer and its upregulation inhibits pancreatic cancer invasion but increases cell proliferation. Mol Cancer2010;9:169.PubMedCrossRef

33.

Loboda A, Nebozhyn MV, Watters JW, Buser CA, Shaw PM, Huang PS, Van't Veer L, Tollenaar RA, Jackson DB, Agrawal D, Dai H, Yeatman TJ. EMT is the dominant program in human colon cancer. BMC Med Genomics2011;4:9.PubMed

34.

Liu W, Zabirnyk O, Wang H, Shiao YH, Nickerson ML, Khalil S, Anderson LM, Perantoni AO, Phang JM. miR-23b targets proline oxidase, a novel tumor suppressor protein in renal cancer. Oncogene2010 Sep 2;29(35):4914–24.PubMedCrossRef

35.

Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A. Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci U S A2009 Feb 3;106(5):1502–5.PubMedCrossRef

36.

Schulte JH, Marschall T, Martin M, Rosenstiel P, Mestdagh P, Schlierf S, Thor T, Vandesompele J, Eggert A, Schreiber S, Rahmann S, Schramm A. Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma. Nucleic Acids Res2010 Sep 1;38(17):5919–28.PubMedCrossRef

37.

Yang JS, Phillips MD, Betel D, Mu P, Ventura A, Siepel AC, Chen KC, Lai EC. Widespread regulatory activity of vertebrate microRNA* species. RNA2011 Feb;17(2):312–26.PubMedCrossRef

Title: Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma
Authors: Dung-Tsa Chen
Jonathan M. Hernandez
David Shibata
Susan M. McCarthy
Leigh Ann Humphries
Whalen Clark
Abul Elahi
Mike Gruidl
Domenico Coppola
Timothy Yeatman
Publication date: 01-05-2012
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 5/2012
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-011-1815-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Complementary Strand MicroRNAs Mediate Acquisition of Metastatic Potential in Colonic Adenocarcinoma

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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