Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Online
ISSN
1689-1392
See all formats and pricing
More options …
Volume 20, Issue 5

Issues

In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer

Manish Patel
  • Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, C/o B.V. Patel PERD Centre, Thaltej, Ahmedabad-380054, Gujarat, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bhavesh Antala
  • Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, C/o B.V. Patel PERD Centre, Thaltej, Ahmedabad-380054, Gujarat, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Neeta Shrivastava
  • Corresponding author
  • Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, C/o B.V. Patel PERD Centre, Thaltej, Ahmedabad-380054, Gujarat, India
  • Department of Pharmacognosy and Phytochemistry, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S. G. Highway, Thaltej, Ahmedabad-380054, Gujarat, India
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-03-05 | DOI: https://doi.org/10.1515/cmble-2015-0046

Abstract

Cell competition is identified as a crucial phenomenon for cancer and organ development. There is a possibility that microRNAs (miRNAs) may play an important role in the regulation of expression of genes involved in cell competition. In silico screening of miRNAs is an effort to abridge, economize and expedite the experimental approaches to identification of potential miRNAs involved in cell competition, as no study has reported involvement of miRNAs in cell competition to date. In this study, we used multiple screening steps as follows: (i) selection of cell competition related genes of Drosophila through a literature survey; (ii) homology study of selected cell competition related genes; (iii) identification of miRNAs that target conserved cell competitionrelated genes through prediction tools; (iv) sequence conservation analysis of identified miRNAs with human genome; (v) identification of conserved cell competition miRNAs using their expression profiles and exploration of roles of their homologous human miRNAs. This study led to the identification of nine potential cell competition miRNAs in the Drosophila genome. Importantly, eighteen human homologs of these nine potential Drosophila miRNAs are well reported for their involvement in different types of cancers. This confirms their probable involvement in cell competition as well, because cell competition is well justified for its involvement in cancer initiation and maintenance.

Keywords: Cancer; MicroRNA; Drosophila melanogaster; Cell competition; Organ development; PITA Top; PicTar; TargetScan; FlyAtlas; ClustalW

References

  • 1. Moreno, E. Is cell competition relevant to cancer? Nat. Rev. Cancer 8 (2008) 141-147.CrossrefGoogle Scholar

  • 2. de la Cova, C., Abril, M., Bellosta, P., Gallant, P. and Johnston, L.A. Drosophila myc regulates organ size by inducing cell competition. Cell 117 (2004) 107-116.CrossrefGoogle Scholar

  • 3. Tamori, Y. and Deng, W.M. Cell competition and its implications for development and cancer. J. Genet. Genomics 38 (2011) 483-495.CrossrefGoogle Scholar

  • 4. Baker, N.E. and Li, W. Cell competition and its possible relation to cancer. Cancer Res. 68 (2008) 5505-5507.CrossrefGoogle Scholar

  • 5. Wagstaff, L., Kolahgar, G. and Piddini, E. Competitive cell interactions in cancer: a cellular tug of war. Trends Cell Biol. 23 (2013) 160-167.CrossrefGoogle Scholar

  • 6. Tamori, Y. and Deng, W.M. Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Dev. Cell 25 (2013) 350-363.CrossrefGoogle Scholar

  • 7. Vincent, J.P., Kolahgar, G., Gagliardi, M. and Piddini, E. Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Dev. Cell 21 (2011) 366-374.CrossrefGoogle Scholar

  • 8. Tyler, D.M., Li, W., Zhuo, N., Pellock, B. and Baker, N.E. Genes affecting cell competition in Drosophila. Genetics 175 (2007) 643-657.CrossrefGoogle Scholar

  • 9. Chen, C.L., Schroeder, M.C., Kango-Singh, M., Tao, C. and Halder, G. Tumor suppression by cell competition through regulation of the Hippo pathway. Proc. Natl. Acad. Sci. U. S. A. 109 (2012) 484-489.CrossrefGoogle Scholar

  • 10. Moreno, E. and Basler, K. dMyc transforms cells into super-competitors. Cell 117 (2004) 117-129.CrossrefGoogle Scholar

  • 11. Graves, H.K., Woodfield, S.E., Yang, C.C., Halder, G. and Bergmann, A. Notch signaling activates Yorkie non-cell autonomously in Drosophila. PLoS One 7 (2012) e37615.CrossrefGoogle Scholar

  • 12. Ohsawa, S., Sugimura, K., Takino, K., Xu, T., Miyawaki, A. and Igaki, T. Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev. Cell 20 (2011) 315-328.CrossrefGoogle Scholar

  • 13. Grzeschik, N.A., Parsons, L.M. and Richardson, H.E. Lgl, the SWH pathway and tumorigenesis: It's a matter of context & competition! Cell Cycle 9 (2010) 3202-3212.Google Scholar

  • 14. Tamori, Y., Bialucha, C.U., Tian, A.G., Kajita, M., Huang, Y.C., Norman, M., Harrison, N., Poulton, J., Ivanovitch, K., Disch, L., Liu, T., Deng, W.M. and Fujita, Y. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 8 (2010) e1000422.CrossrefGoogle Scholar

  • 15. Li, W. and Baker, N.E. Engulfment is required for cell competition. Cell 129 (2007) 1215-1225.CrossrefGoogle Scholar

  • 16. Xiong, H., Qian, J., He, T. and Li, F. Independent transcription of miR-281 in the intron of ODA in Drosophila melanogaster. Biochem. Biophys. Res. Commun. 378 (2009) 883-889.Google Scholar

  • 17. Engelmann, J.C. and Spang, R. A least angle regression model for the prediction of canonical and non-canonical miRNA-mRNA interactions. PLoS One 7 (2012) e40634.CrossrefGoogle Scholar

  • 18. Fullaondo, A. and Lee, S.Y. Identification of putative miRNA involved in Drosophila melanogaster immune response. Dev. Comp. Immunol. 36 (2012) 267-273.CrossrefGoogle Scholar

  • 19. Huang da, W., Sherman, B.T. and Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4 (2009) 44-57.Google Scholar

  • 20. Huang da, W., Sherman, B.T. and Lempicki, R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37 (2009) 1-13.CrossrefGoogle Scholar

  • 21. Shirdel, E.A., Xie, W., Mak, T.W. and Jurisica, I. NAViGaTing the micronome--using multiple microRNA prediction databases to identify signalling pathway-associated microRNAs. PLoS One 6 (2011) e17429.CrossrefGoogle Scholar

  • 22. Witkos, T.M., Koscianska, E. and Krzyzosiak, W.J. Practical Aspects of microRNA Target Prediction. Curr. Mol. Med. 11 (2011) 93-109.CrossrefGoogle Scholar

  • 23. Ibanez-Ventoso, C., Vora, M. and Driscoll, M. Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PLoS One 3 (2008) e2818.CrossrefGoogle Scholar

  • 24. Thompson, J.D., Higgins, D.G. and Gibson, T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22 (1994) 4673-4680.CrossrefGoogle Scholar

  • 25. de Beco, S., Ziosi, M. and Johnston, L.A. New frontiers in cell competition. Dev. Dyn. 241 (2012) 831-841.Google Scholar

  • 26. Yuan, L., Hillman, J.D. and Progulske-Fox, A. Microarray analysis of quorum-sensing-regulated genes in Porphyromonas gingivalis. Infect. Immun. 73 (2005) 4146-4154. CrossrefGoogle Scholar

  • 27. Igaki, T., Pastor-Pareja, J.C., Aonuma, H., Miura, M. and Xu, T. Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev. Cell 16 (2009) 458-465.CrossrefGoogle Scholar

  • 28. Kuranaga, E., Kanuka, H., Igaki, T., Sawamoto, K., Ichijo, H., Okano, H. and Miura, M. Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. Nat. Cell Biol. 4 (2002) 705-710.CrossrefGoogle Scholar

  • 29. Moreno, E., Basler, K. and Morata, G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416 (2002) 755-759.CrossrefGoogle Scholar

  • 30. Suissa, Y., Ziv, O., Dinur, T., Arama, E. and Gerlitz, O. The NAB-Brk signal bifurcates at JNK to independently induce apoptosis and compensatory proliferation. J. Biol. Chem. 286 (2011) 15556-15564.CrossrefGoogle Scholar

  • 31. Li, W., You, L., Cooper, J., Schiavon, G., Pepe-Caprio, A., Zhou, L., Ishii, R., Giovannini, M., Hanemann, C.O., Long, S.B., Erdjument-Bromage, H., Zhou, P., Tempst, P. and Giancotti, F.G. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell 140 (2010) 477-490.Google Scholar

  • 32. Neto-Silva, R.M., de Beco, S. and Johnston, L.A. Evidence for a growthstabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Dev. Cell 19 (2010) 507-520.CrossrefGoogle Scholar

  • 33. Prober, D.A. and Edgar, B.A. Ras1 promotes cellular growth in the Drosophila wing. Cell 100 (2000) 435-446.CrossrefGoogle Scholar

  • 34. Vaccari, T. and Bilder, D. The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating notch trafficking. Dev. Cell 9 (2005) 687-698.CrossrefGoogle Scholar

  • 35. Giraldez, A.J. and Cohen, S.M. Wingless and Notch signaling provide cell survival cues and control cell proliferation during wing development. Development 130 (2003) 6533-6543.CrossrefGoogle Scholar

  • 36. Moberg, K.H., Schelble, S., Burdick, S.K. and Hariharan, I.K. Mutations in erupted, the Drosophila ortholog of mammalian tumor susceptibility gene 101, elicit non-cell-autonomous overgrowth. Dev. Cell 9 (2005) 699-710.CrossrefGoogle Scholar

  • 37. Vidal, M., Larson, D.E. and Cagan, R.L. Csk-deficient boundary cells are eliminated from normal Drosophila epithelia by exclusion, migration, and apoptosis. Dev. Cell 10 (2006) 33-44.CrossrefGoogle Scholar

  • 38. Rhiner, C., Lopez-Gay, J.M., Soldini, D., Casas-Tinto, S., Martin, F.A., Lombardia, L. and Moreno, E. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 18 (2010) 985-998.CrossrefGoogle Scholar

  • 39. Portela, M., Casas-Tinto, S., Rhiner, C., Lopez-Gay, J.M., Dominguez, O., Soldini, D. and Moreno, E. Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev. Cell 19 (2010) 562-573. CrossrefGoogle Scholar

  • 40. Ruby, J.G., Stark, A., Johnston, W.K., Kellis, M., Bartel, D.P. and Lai, E.C. Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAs. Genome Res. 17 (2007) 1850-1864.CrossrefGoogle Scholar

  • 41. Lai, E.C., Tomancak, P., Williams, R.W. and Rubin, G.M. Computational identification of Drosophila microRNA genes. Genome Biol. 4 (2003) R42.CrossrefGoogle Scholar

  • 42. Lim, L.P., Lau, N.C., Weinstein, E.G., Abdelhakim, A., Yekta, S., Rhoades, M.W., Burge, C.B. and Bartel, D.P. The microRNAs of Caenorhabditis elegans. Genes Dev. 17 (2003) 991-1008.CrossrefGoogle Scholar

  • 43. Levayer, R. and Moreno, E. Mechanisms of cell competition: themes and variations. J. Cell Biol. 200 (2013) 689-698.Google Scholar

  • 44. Pandey, U.B. and Nichols, C.D. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol. Rev. 63 (2011) 411-436.CrossrefGoogle Scholar

  • 45. Rhiner, C. and Moreno, E. Super competition as a possible mechanism to pioneer precancerous fields. Carcinogenesis 30 (2009) 723-728.CrossrefGoogle Scholar

  • 46. Casas-Tinto, S., Torres, M. and Moreno, E. The flower code and cancer development. Clin. Transl. Oncol. 13 (2011) 5-9.CrossrefGoogle Scholar

  • 47. Gottardo, F., Liu, C.G., Ferracin, M., Calin, G.A., Fassan, M., Bassi, P., Sevignani, C., Byrne, D., Negrini, M., Pagano, F., Gomella, L.G., Croce, C.M. and Baffa, R. Micro-RNA profiling in kidney and bladder cancers. Urol. Oncol. 25 (2007) 387-392.CrossrefGoogle Scholar

  • 48. Wang, X., Tang, S., Le, S.Y., Lu, R., Rader, J.S., Meyers, C. and Zheng, Z.M. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3 (2008) e2557.CrossrefGoogle Scholar

  • 49. Liu, T., Tang, H., Lang, Y., Liu, M. and Li, X. MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett. 273 (2009) 233-242.Google Scholar

  • 50. Mertens-Talcott, S.U., Chintharlapalli, S., Li, X. and Safe, S. The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 67 (2007) 11001-11011.CrossrefGoogle Scholar

  • 51. Guttilla, I.K. and White, B.A. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J. Biol. Chem. 284 (2009) 23204-23216.Google Scholar

  • 52. Mu, W., Hu, C., Zhang, H., Qu, Z., Cen, J., Qiu, Z., Li, C., Ren, H., Li, Y., He, X., Shi, X. and Hui, L. miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 25 (2015) 477-495.Google Scholar

  • 53. Li, M., Fu, W., Wo, L., Shu, X., Liu, F. and Li, C. miR-128 and its target genes in tumorigenesis and metastasis. Exp. Cell Res. 319 (2013) 3059-3064.CrossrefGoogle Scholar

  • 54. Schraivogel, D., Weinmann, L., Beier, D., Tabatabai, G., Eichner, A., Zhu, J.Y., Anton, M., Sixt, M., Weller, M., Beier, C.P. and Meister, G. CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells. EMBO J. 30 (2011) 4309-4322. Google Scholar

  • 55. Hsieh, I.S., Chang, K.C., Tsai, Y.T., Ke, J.Y., Lu, P.J., Lee, K.H., Yeh, S.D., Hong, T.M. and Chen, Y.L. MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/betacatenin signaling pathway. Carcinogenesis 34 (2013) 530-538.CrossrefGoogle Scholar

  • 56. Hong, L., Lai, M., Chen, M., Xie, C., Liao, R., Kang, Y.J., Xiao, C., Hu, W.Y., Han, J. and Sun, P. The miR-17-92 cluster of microRNAs confers tumorigenicity by inhibiting oncogene-induced senescence. Cancer Res. 70 (2010) 8547-8557.Google Scholar

  • 57. Chen, Q., Li, L., Tu, Y., Zheng, L.L., Liu, W., Zuo, X.Y., He, Y.M., Zhang, S.Y., Zhu, W., Cao, J.P., Cui, F.M. and Hou, J. MiR-34a regulates apoptosis in liver cells by targeting the KLF4 gene. Cell. Mol. Biol. Lett. 19 (2014) 52-64.Google Scholar

  • 58. Afanasyeva, E.A., Mestdagh, P., Kumps, C., Vandesompele, J., Ehemann, V., Theissen, J., Fischer, M., Zapatka, M., Brors, B., Savelyeva, L., Sagulenko, V., Speleman, F., Schwab, M. and Westermann, F. MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ. 18 (2011) 974-984.Google Scholar

  • 59. Selcuklu, S.D., Donoghue, M.T., Rehmet, K., de Souza Gomes, M., Fort, A., Kovvuru, P., Muniyappa, M.K., Kerin, M.J., Enright, A.J. and Spillane, C. MicroRNA-9 inhibition of cell proliferation and identification of novel miR-9 targets by transcriptome profiling in breast cancer cells. J. Biol. Chem. 287 (2012) 29516-29528.Google Scholar

  • 60. Sun, Q., Luo, T., Ren, Y., Florey, O., Shirasawa, S., Sasazuki, T., Robinson, D.N. and Overholtzer, M. Competition between human cells by entosis. Cell Res. 24 (2014) 1299-1310. CrossrefGoogle Scholar

About the article

Received: 2015-05-30

Accepted: 2015-10-20

Published Online: 2016-03-05

Published in Print: 2015-12-01


Citation Information: Cellular and Molecular Biology Letters, Volume 20, Issue 5, Pages 798–815, ISSN (Online) 1689-1392, DOI: https://doi.org/10.1515/cmble-2015-0046.

Export Citation

© University of Wroclaw, Poland.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Rafal Bartoszewski and Aleksander F. Sikorski
Cellular & Molecular Biology Letters, 2018, Volume 23, Number 1
[2]
Simone Di Giacomo, Manuela Sollazzo, Simona Paglia, and Daniela Grifoni
Genes, 2017, Volume 8, Number 4, Page 120

Comments (0)

Please log in or register to comment.
Log in