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Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

  • Wang, Ning (Department of Computer Science and Technology, Jilin University) ;
  • Xu, Zhi-Wen (Department of Computer Science and Technology, Jilin University) ;
  • Wang, Kun-Hao (Department of Computer Science and Technology, Jilin University)
  • Published : 2015.01.06

Abstract

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Materials and Methods: Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Results: Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. Conclusions: The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

Keywords

References

  1. Abdel-Rahman WM, Ruosaari S, Knuutila S et al (2012). Differential roles of EPS8 in carcinogenesis: Loss of protein expression in a subset of colorectal carcinoma and adenoma. WJG, 18, 3896-903. https://doi.org/10.3748/wjg.v18.i29.3896
  2. Arroyo JD, Chevillet JR, Kroh EM et al (2011). Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. PNAS, 108, 5003-8. https://doi.org/10.1073/pnas.1019055108
  3. Baskerville S, Bartel DP (2005). Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11, 241-7. https://doi.org/10.1261/rna.7240905
  4. Belkin DA, Mitsui H, Wang CQ et al (2013). CD200 Upregulation in Vascular Endothelium Surrounding Cutaneous Squamous Cell Carcinoma. JAMA Dermatol, 149, 178-86. https://doi.org/10.1001/jamadermatol.2013.1609
  5. Botti E, Spallone G, Moretti F et al (2011). Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. PNAS, 108, 13710-5. https://doi.org/10.1073/pnas.1110931108
  6. Boukamp P (2005). Non-melanoma skin cancer: what drives tumor development and progression?. Carcinogenesis, 26, 1657-67. https://doi.org/10.1093/carcin/bgi123
  7. Bruegger C, Kempf W, Spoerri I et al (2013). MicroRNA expression differs in cutaneous squamous cell carcinomas and healthy skin of immunocompetent individuals. Exp Dermatol, 22, 426-8. https://doi.org/10.1111/exd.12153
  8. Butani A, Arbesfeld DM, Schwartz RA (2005). Premalignant and early squamous cell carcinoma. Clin Plast Surg, 32, 223. https://doi.org/10.1016/j.cps.2004.11.001
  9. Calin GA, Croce CM (2006). MicroRNA signatures in human cancers. Nat Rev Cancer, 6, 857-66. https://doi.org/10.1038/nrc1997
  10. Cao G, Huang B, Liu Z et al (2010). Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways. Biochem Bioph Res Co, 396, 978-82. https://doi.org/10.1016/j.bbrc.2010.05.037
  11. Chakraborty S, Swanson BJ, Bonthu N et al (2010). Aberrant upregulation of MUC4 mucin expression in cutaneous condyloma acuminatum and squamous cell carcinoma suggests a potential role in the diagnosis and therapy of skin diseases. J Clin Pathol, 63, 579-84. https://doi.org/10.1136/jcp.2010.076125
  12. Chang SS, Smith I, Glazer C et al (2010). EIF2C Is Overexpressed and Amplified in Head and Neck Squamous Cell Carcinoma. Orl J Oto-Rhino-Lary, 72, 337-43.
  13. Chakraborty S, Swanson BJ, Bonthu N et al (2012). Differential expression of Fas family members and Bcl-2 family members in benign versus malignant epithelial ovarian cancer (EOC) in North Indian population. Mol Cell Biochem, 368, 119-26. https://doi.org/10.1007/s11010-012-1350-7
  14. Chen YJ, Wu CY, Chang CC et al (2008). Nuclear Kruppel-like factor 4 expression is associated with human skin squamous cell carcinoma progression and metastasis. Cancer Biol Ther, 7, 777-82. https://doi.org/10.4161/cbt.7.5.5768
  15. Croce CM (2009). Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet, 10, 704-14. https://doi.org/10.1038/nrg2634
  16. Dang C, Gottschling M, Manning K et al (2006). Identification of dysregulated genes in cutaneous squamous cell carcinoma. Oncol Rep, 16, 513-9.
  17. Das GD, Bhattacharjee B, Sen S et al (2012). Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions. Plos One, 7, 44678. https://doi.org/10.1371/journal.pone.0044678
  18. Endo-Munoz L, Dahler A, Teakle N et al (2009). E2F7 can regulate proliferation, differentiation, and apoptotic responses in human keratinocytes: implications for cutaneous squamous cell carcinoma formation. Cancer Res, 69, 1800-8. https://doi.org/10.1158/0008-5472.CAN-08-2725
  19. Enerly E, Steinfeld I, Kleivi K et al (2011). miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors. Plos One, 6, 16915. https://doi.org/10.1371/journal.pone.0016915
  20. Griewank KG, Murali R, Schilling B et al (2013). TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma. Plos One, 8, 80354. https://doi.org/10.1371/journal.pone.0080354
  21. Hameetman L, Commandeur S, Bavinck JN et al (2013). Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients. BMC Cancer, 13, 58. https://doi.org/10.1186/1471-2407-13-58
  22. Heah KG1, Hassan MI, Huat SC (2011). p53 Expression as a Marker of Microinvasion in Oral Squamous Cell Carcinoma. Asian Pac J Cancer P, 12, 1017-22.
  23. Hsu SD, Lin FM, Wu WY et al (2011). Hsu SD, Lin FM, Wu WY et al: miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res, 39, 163-9. https://doi.org/10.1093/nar/gkq1107
  24. Huber MA, Kraut N, Beug H (2005). Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol, 17, 548-58. https://doi.org/10.1016/j.ceb.2005.08.001
  25. Inui M, Martello G, Piccolo S (2010). MicroRNA control of signal transduction. Nat Rev Mol Cell Bio, 11, 252-63. https://doi.org/10.1038/nrn2804
  26. Iorio MV, Ferracin M, Liu CG et al (2005). MicroRNA gene expression deregulation in human breast cancer. Cancer Res, 65, 7065-70. https://doi.org/10.1158/0008-5472.CAN-05-1783
  27. Johnson SM, Grosshans H, Shingara J et al (2005). RAS is regulated by the let-7 microRNA family. Cell, 120, 635-47. https://doi.org/10.1016/j.cell.2005.01.014
  28. Karin M (1990). Too many transcription factors: positive and negative interactions. New Biol, 2, 126-31.
  29. Kathpalia VP, Mussak EN, Chow SS et al (2006). Genome-wide transcriptional profiling in human squamous cell carcinoma of the skin identifies unique tumor-associated signatures. J Dermatol, 33, 309-18. https://doi.org/10.1111/j.1346-8138.2006.00075.x
  30. Kim SW, Ramasamy K, Bouamar H et al (2012). MicroRNAs miR-125a and miR-125b constitutively activate the NFkappa B pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). PNAS, 109, 7865-70. https://doi.org/10.1073/pnas.1200081109
  31. Kozomara A, Griffiths-Jones S. (2011). miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res, 39, 152-7.
  32. Latchman DS (1997). Transcription factors: an overview. Int J Biochem Cell Biol, 29, 1305-12. https://doi.org/10.1016/S1357-2725(97)00085-X
  33. Le MT, Shyh-Chang N, Khaw SL et al (2011). Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving mirna-target gene pairs. Plos Genet, 7, 1002242. https://doi.org/10.1371/journal.pgen.1002242
  34. Le MT, Teh C, Shyh-Chang N et al (2009). MicroRNA-125b is a novel negative regulator of p53. Gene Dev, 23, 862-76. https://doi.org/10.1101/gad.1767609
  35. Lee YS, Kim HK, Chung SM et al (2005). Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the downregulation of putative targets during differentiation. J Biol Chem, 280, 16635-41. https://doi.org/10.1074/jbc.M412247200
  36. Lefort K, Brooks Y, Ostano P et al (2013). A miR-34a-SIRT6 axis in the squamous cell differentiation network. EMBO J, 32, 2248-63. https://doi.org/10.1038/emboj.2013.156
  37. Li Y, Guessous F, Zhang Y et al (2009). MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res, 69, 7569-76. https://doi.org/10.1158/0008-5472.CAN-09-0529
  38. Libermann TA, Zerbini LF (2006). Targeting transcription factors for cancer gene therapy. Curr Gene Ther, 6, 17-33. https://doi.org/10.2174/156652306775515501
  39. Loeb KR, Asgari MM, Hawes SE et al (2012). Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas. Plos One, 7, 34422. https://doi.org/10.1371/journal.pone.0034422
  40. Lu J, Getz G, Miska EA et al (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834-8. https://doi.org/10.1038/nature03702
  41. Mandinova A, Kolev V, Neel V, et al (2009). A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans. J Clin Invest, 119, 3127-37. https://doi.org/10.1172/JCI38543
  42. Michael MZ, O' Connor SM, van Holst Pellekaan NG et al (2003). Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res, 1, 882-91.
  43. Moad AI, Tan ML, Kaur G et al (2012). Lack of increased P15INK4B protein expression in basal cell carcinomas. Asian Pac J Cancer Prev, 13, 6239-44. https://doi.org/10.7314/APJCP.2012.13.12.6239
  44. Moad AI, Lan TM, Kaur G, et al (2009). Immunohistochemical determination of the P15 (INK4b) protein expression in cutaneous squamous cell carcinoma. J Cutan Pathol, 36, 183-9. https://doi.org/10.1111/j.1600-0560.2008.00989.x
  45. Nam EJ, Yoon H, Kim SW et al (2008). MicroRNA expression profiles in serous ovarian carcinoma. Clin Cancer Res, 14, 2690-5. https://doi.org/10.1158/1078-0432.CCR-07-1731
  46. Park E, Liu B, Xia X et al (2011). Role of IKK alpha in skin squamous cell carcinomas. Future Oncol, 7, 123-34. https://doi.org/10.2217/fon.10.166
  47. Petitjean A, Achatz MI, Borresen-Dale AL et al (2007). TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene, 26, 2157-65. https://doi.org/10.1038/sj.onc.1210302
  48. Petitjean A, Mathe E, Kato S et al (2007). Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum Mutat, 28, 622-9. https://doi.org/10.1002/humu.20495
  49. Polakis P (2000). Wnt signaling and cancer. Gene Dev, 14, 1837-51.
  50. Poliseno L, Salmena L, Riccardi L et al (2010). Identification of the miR-106b-25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation. Sci Signal, 3, 29.
  51. Qu H, Xu W, Huang Y et al (2011). Circulating miRNAs: promising biomarkers of human cancer. Asian Pac J Cancer Prev, 12, 1117-25.
  52. Raver-Shapira N, Marciano E, Meiri E et al (2007). Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell, 26, 731-43. https://doi.org/10.1016/j.molcel.2007.05.017
  53. Rodriguez A, Griffiths-Jones S, Ashurst JL et al (2004). Identification of mammalian microRNA host genes and transcription units. Genome Res, 14, 1902-10. https://doi.org/10.1101/gr.2722704
  54. Sand M, Skrygan M, Georgas D et al (2012). Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinogen, 51, 916-22. https://doi.org/10.1002/mc.20861
  55. Sand M, Skrygan M, Georgas D et al (2012). Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma. J Dermatol Sci, 68, 119-26. https://doi.org/10.1016/j.jdermsci.2012.09.004
  56. Sethupathy P, Corda B, Hatzigeorgiou AG et al (2006). TarBase: A comprehensive database of experimentally supported animal microRNA targets. RNA, 12, 192-7.
  57. Soussi T, Beroud C (2001). Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer, 1, 233-40. https://doi.org/10.1038/35106009
  58. Sowalsky AG, Alt-Holland A, Shamis Y et al (2010). RalA suppresses early stages of Ras-induced squamous cell carcinoma progression. Oncogene, 29, 45-55. https://doi.org/10.1038/onc.2009.307
  59. Suzuki HI, Yamagata K, Sugimoto K et al (2009). Modulation of microRNA processing by p53. Nature, 460, 529-111. https://doi.org/10.1038/nature08199
  60. Toriseva M, Ala-aho R, Peltonen S et al (2012). Keratinocyte Growth Factor Induces Gene Expression Signature Associated with Suppression of Malignant Phenotype of Cutaneous Squamous Carcinoma Cells. Plos One, 7, 33041. https://doi.org/10.1371/journal.pone.0033041
  61. Volinia S, Calin GA, Liu CG et al (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. PNAS, 103, 2257-61. https://doi.org/10.1073/pnas.0510565103
  62. Wang J, Lu M, Qiu C et al (2010). TransmiR: a transcription factor-microRNA regulation database. Nucleic Acids Res 38: D119-122, 2010. Nucleic Acids Res, 38, 119-22.
  63. Wang NJ, Sanborn Z, Arnett KL et al (2011). Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. PNAS, 108, 17761-6. https://doi.org/10.1073/pnas.1114669108
  64. Wu Di, Guo Ze, Min Wei et al (2012). Upregulation of TCTP expression in human skin squamous cell carcinoma increases tumor cell viability through anti-apoptotic action of the protein. Exp Ther Med, 3, 437-42.
  65. Wu J, Zheng C, Fan Y et al (2014). Downregulation of MicroRNA-30 Facilitates Podocyte Injury and Is Prevented by Glucocorticoids. J Am Soc Nephrol, 25, 92-104. https://doi.org/10.1681/ASN.2012111101
  66. Xia YH, Li M, Fu DD et al (2013). Effects of PTTG downregulation on proliferation and metastasis of the SCL-1 cutaneous squamous cell carcinoma cell Line. Asian Pac J Cancer Prev, 14, 6245-8. https://doi.org/10.7314/APJCP.2013.14.11.6245
  67. Xie YJ, Long ZF, He XS (2013). Involvement of EBV-encoded BART-miRNAs and dysregulated cellular miRNAs in nasopharyngeal carcinoma genesis. Asian Pac J Cancer Prev, 14, 5637-44. https://doi.org/10.7314/APJCP.2013.14.10.5637
  68. Xu N, Zhang L, Meisgen F et al (2012). MicroRNA-125b Downregulates Matrix Metallopeptidase 13 and Inhibits Cutaneous Squamous Cell Carcinoma Cell Proliferation, Migration, and Invasion. J Biol Chem, 287, 29899-908. https://doi.org/10.1074/jbc.M112.391243
  69. Yadav V, Yanez NC, Fenton SE et al (2010). Loss of protein kinase C delta gene expression in human squamous cell carcinomas - a laser capture microdissection study. Am J Pathol, 176, 1091-6. https://doi.org/10.2353/ajpath.2010.090816
  70. Yamakuchi M, Lowenstein CJ (2009). MiR-34, SIRT1 and p53 The feedback loop. Cell Cycle, 8, 712-5. https://doi.org/10.4161/cc.8.5.7753
  71. Yin VT1, Pfeiffer ML, Esmaeli B (2013). Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthal Plast Recons, 29, 87-92. https://doi.org/10.1097/IOP.0b013e3182831bf3
  72. Zheng DJ, Yu GH, Gao JF et al (2013). Concomitant EGFR inhibitors combined with radiation for treatment of nonsmall cell lung carcinoma. Asian Pac J Cancer Prev, 14, 4485-94. https://doi.org/10.7314/APJCP.2013.14.8.4485

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