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MiR-21 and miR-205 are induced in invasive cutaneous squamous cell carcinomas

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Abstract

Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of keratinocytes with an uncertain molecular basis causing significant morbidity. MicroRNAs (miRs) are small RNA molecules that regulate gene expression on post- transcriptional level. MiRs are critical to various biological processes. To determine if miRs play a role in pathogenesis of invasive cSCC, we collected patients’ specimens from in situ and invasive cSCC (n = 19) and examined miRs expression levels using qPCR. Specifically, we evaluated miR-21, miR-103a, miR-186, miR-200b, miR-203, and miR-205 expression levels due to their role in skin biology and epithelial to mesenchymal transition. MiR levels were compared between in situ and invasive cSCCs. We found statistically significant (p ≤ 0.05) upregulation of miR-21 and miR-205 in invasive cSCC compared to cSCC in situ. We concluded that miR-21 and miR-205 may have diagnostic value in determining the invasive properties of cSCCs and that each cSCC displays unique miR profile, underscoring the possibility of personalized medicine approach in developing potential novel, less invasive treatments.

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References

  1. Alam MRD (2001) Cutaneous squamous-cell carcinoma. N Engl J Med 13:975–983

    Article  Google Scholar 

  2. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355. doi:10.1038/nature02871

    Article  CAS  PubMed  Google Scholar 

  3. Baffa R, Fassan M, Volinia S, O’Hara B, Liu CG, Palazzo JP, Gardiman M, Rugge M, Gomella LG, Croce CM, Rosenberg A (2009) MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 219:214–221. doi:10.1002/path.2586

    Article  CAS  PubMed  Google Scholar 

  4. Bostjancic E, Glavac D (2008) Importance of microRNAs in skin morphogenesis and diseases. Acta Dermatovenerol Alp Panon Adriat 17:95–102

    Google Scholar 

  5. Bruegger C, Kempf W, Spoerri I, Arnold AW, Itin PH, Burger B (2013) MicroRNA expression differs in cutaneous squamous cell carcinomas and healthy skin of immunocompetent individuals. Exp Dermatol 22:426–428. doi:10.1111/exd.12153

    Article  CAS  PubMed  Google Scholar 

  6. Chen B, Pan W, Lin X, Hu Z, Jin Y, Chen H, Ma G, Qiu Y, Chang L, Hua C, Zou Y, Gao Y, Ying H, Lv D (2015) MicroRNA-346 functions as an oncogene in cutaneous squamous cell carcinoma. Tumour Biol. doi:10.1007/s13277-015-4046-2

    Google Scholar 

  7. Chen D, Yan W, Liu Z, Zhang Z, Zhu L, Liu W, Ding X, Wang A, Chen Y (2016) Downregulation of miR-221 enhances the sensitivity of human oral squamous cell carcinoma cells to Adriamycin through upregulation of TIMP3 expression. Biomed Pharmacother 77:72–78. doi:10.1016/j.biopha.2015.12.002

    Article  CAS  PubMed  Google Scholar 

  8. Chen S, Zhu J, Yu F, Tian Y, Ma S, Liu X (2015) Combination of miRNA and RNA functions as potential biomarkers for gastric cancer. Tumour Biol 36:9909–9918. doi:10.1007/s13277-015-3756-9

    Article  CAS  PubMed  Google Scholar 

  9. Cheng YX, Chen GT, Chen C, Zhang QF, Pan F, Hu M, Li BS (2016) MicroRNA-200b inhibits epithelial-mesenchymal transition and migration of cervical cancer cells by directly targeting RhoE. Mol Med Rep. doi:10.3892/mmr.2016.4933

    Google Scholar 

  10. Cherpelis BS, Marcusen C, Lang PG (2002) Prognostic factors for metastasis in squamous cell carcinoma of the skin. Dermatol Surg 28:268–273

    PubMed  Google Scholar 

  11. Dong W, Yongjun L, Nan D, Junyun W, Qiong Y, Yaran Y, Yanming L, Xiangdong F, Hua Z (2015) Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line. Yi Chuan 37:673–682. doi:10.16288/j.yczz.15-022

    PubMed  Google Scholar 

  12. Dziunycz P, Iotzova-Weiss G, Eloranta JJ, Lauchli S, Hafner J, French LE, Hofbauer GF (2010) Squamous cell carcinoma of the skin shows a distinct microRNA profile modulated by UV radiation. J Investig Dermatol 130:2686–2689. doi:10.1038/jid.2010.169

    Article  CAS  PubMed  Google Scholar 

  13. Elsnerova K, Mohelnikova-Duchonova B, Cerovska E, Ehrlichova M, Gut I, Rob L, Skapa P, Hruda M, Bartakova A, Bouda J, Vodicka P, Soucek P, Vaclavikova R (2016) Gene expression of membrane transporters: importance for prognosis and progression of ovarian carcinoma. Oncol Rep. doi:10.3892/or.2016.4599

    PubMed  Google Scholar 

  14. Foundation TSC (2016). http://www.skincancer.org/skin-cancer-information/skin-cancer-facts. Accessed 8 June 2016

  15. Gao W, Shen H, Liu L, Xu J, Xu J, Shu Y (2011) MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. J Cancer Res Clin Oncol 137:557–566. doi:10.1007/s00432-010-0918-4

    Article  CAS  PubMed  Google Scholar 

  16. He W, Zhang MG, Wang XJ, Zhong S, Shao Y, Zhu Y, Shen ZJ (2013) KAT5 and KAT6B are in positive regulation on cell proliferation of prostate cancer through PI3K-AKT signaling. Int J Clin Exp Pathol 6:2864–2871

    PubMed  PubMed Central  Google Scholar 

  17. Centers for Disease Control and Prevention (2016). http://www.cdc.gov/cancer/skin/statistics/race.htm. Accessed 20 Aug 2016

  18. Huang Y, Kesselman D, Kizub D, Guerrero-Preston R, Ratovitski EA (2013) Phospho-deltaNp63alpha/microRNA feedback regulation in squamous carcinoma cells upon cisplatin exposure. Cell Cycle 12:684–697. doi:10.4161/cc.23598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hufbauer M, Lazic D, Reinartz M, Akgul B, Pfister H, Weissenborn SJ (2011) Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets. J Dermatol Sci 64:7–15. doi:10.1016/j.jdermsci.2011.06.008

    Article  CAS  PubMed  Google Scholar 

  20. Karia PS, Han J, Schmults CD (2013) Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol 68:957–966. doi:10.1016/j.jaad.2012.11.037

    Article  PubMed  Google Scholar 

  21. Kramer A, Green J, Pollard J Jr, Tugendreich S (2014) Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30:523–530. doi:10.1093/bioinformatics/btt703

    Article  PubMed  Google Scholar 

  22. Li X, Huang K, Yu J (2014) Inhibition of microRNA-21 upregulates the expression of programmed cell death 4 and phosphatase tensin homologue in the A431 squamous cell carcinoma cell line. Oncol Lett 8:203–207. doi:10.3892/ol.2014.2066

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Liao F, Ji MY, Shen L, Qiu S, Guo XF, Dong WG (2013) Decreased EGR3 expression is related to poor prognosis in patients with gastric cancer. J Mol Histol 44:463–468. doi:10.1007/s10735-013-9493-8

    Article  CAS  PubMed  Google Scholar 

  24. Luo Q, Li W, Zhao T, Tian X, Liu Y, Zhang X (2015) Role of miR-148a in cutaneous squamous cell carcinoma by repression of MAPK pathway. Arch Biochem Biophys 583:47–54. doi:10.1016/j.abb.2015.07.022

    Article  CAS  PubMed  Google Scholar 

  25. Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, Hayashi T, Kunizaki M, Hidaka S, Nagayasu T, Nakashima M, Ujifuku K, Mitsutake N, Ohtsuru A, Yamashita S, Korpal M, Kang Y, Gregory PA, Goodall GJ, Kohno S, Nakao K (2011) MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. J Transl Med 9:30. doi:10.1186/1479-5876-9-30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mitsui H, Suarez-Farinas M, Gulati N, Shah KR, Cannizzaro MV, Coats I, Felsen D, Krueger JG, Carucci JA (2014) Gene expression profiling of the leading edge of cutaneous squamous cell carcinoma: IL-24-driven MMP-7. J Investig Dermatol 134:1418–1427. doi:10.1038/jid.2013.494

    Article  CAS  PubMed  Google Scholar 

  27. Obayashi M, Yoshida M, Tsunematsu T, Ogawa I, Sasahira T, Kuniyasu H, Imoto I, Abiko Y, Xu D, Fukunaga S, Tahara H, Kudo Y, Nagao T, Takata T (2016) microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer. Oncotarget. doi:10.18632/oncotarget.6972

    PubMed  PubMed Central  Google Scholar 

  28. Okamura Y, Nomoto S, Hayashi M, Hishida M, Nishikawa Y, Yamada S, Fujii T, Sugimoto H, Takeda S, Kodera Y, Nakao A (2011) Identification of the bleomycin hydrolase gene as a methylated tumor suppressor gene in hepatocellular carcinoma using a novel triple-combination array method. Cancer Lett 312:150–157. doi:10.1016/j.canlet.2011.07.028

    Article  CAS  PubMed  Google Scholar 

  29. Okumura K, Saito M, Isogai E, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T, Wakabayashi Y (2014) Meis1 regulates epidermal stem cells and is required for skin tumorigenesis. PLoS One 9:e102111. doi:10.1371/journal.pone.0102111

    Article  PubMed  PubMed Central  Google Scholar 

  30. Paiva I, Gil da Costa RM, Ribeiro J, Sousa H, Bastos MM, Faustino-Rocha A, Lopes C, Oliveira PA, Medeiros R (2015) MicroRNA-21 expression and susceptibility to HPV-induced carcinogenesis—role of microenvironment in K14-HPV16 mice model. Life Sci 128:8–14. doi:10.1016/j.lfs.2015.02.020

    Article  CAS  PubMed  Google Scholar 

  31. Pastar I, Khan AA, Stojadinovic O, Lebrun EA, Medina MC, Brem H, Kirsner RS, Jimenez JJ, Leslie C, Tomic-Canic M (2012) Induction of specific microRNAs inhibits cutaneous wound healing. J Biol Chem 287:29324–29335. doi:10.1074/jbc.M112.382135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Patani N, Jiang WG, Newbold RF, Mokbel K (2011) Histone-modifier gene expression profiles are associated with pathological and clinical outcomes in human breast cancer. Anticancer Res 31:4115–4125

    CAS  PubMed  Google Scholar 

  33. Patnaik S, Mallick R, Kannisto E, Sharma R, Bshara W, Yendamuri S, Dhillon SS (2015) MiR-205 and miR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies. J Thorac Oncol 10:446–453. doi:10.1097/JTO.0000000000000423

    Article  CAS  PubMed  Google Scholar 

  34. Petter G, Haustein UF (2000) Histologic subtyping and malignancy assessment of cutaneous squamous cell carcinoma. Dermatol Surg 26:521–530

    Article  CAS  PubMed  Google Scholar 

  35. Pio R, Jia Z, Baron VT, Mercola D, Cancer UNSCotSPftEoCS-P (2013) Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer. PLoS One 8:e54096. doi:10.1371/journal.pone.0054096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sand M, Skrygan M, Georgas D, Sand D, Hahn SA, Gambichler T, Altmeyer P, Bechara FG (2012) Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma. J Dermatol Sci 68:119–126. doi:10.1016/j.jdermsci.2012.09.004

    Article  CAS  PubMed  Google Scholar 

  37. Schwartz DR, Homanics GE, Hoyt DG, Klein E, Abernethy J, Lazo JS (1999) The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance. Proc Natl Acad Sci USA 96:4680–4685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey B, Scheynius A, Stahle M, Pivarcsi A (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2:e610. doi:10.1371/journal.pone.0000610

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sun SS, Zhou X, Huang YY, Kong LP, Mei M, Guo WY, Zhao MH, Ren Y, Shen Q, Zhang L (2015) Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma. Mol Cancer 14:213. doi:10.1186/s12943-015-0487-x

    Article  PubMed  PubMed Central  Google Scholar 

  40. Taube JH, Malouf GG, Lu E, Sphyris N, Vijay V, Ramachandran PP, Ueno KR, Gaur S, Nicoloso MS, Rossi S, Herschkowitz JI, Rosen JM, Issa JP, Calin GA, Chang JT, Mani SA (2013) Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties. Sci Rep 3:2687. doi:10.1038/srep02687

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA (2011) Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck 33:504–512. doi:10.1002/hed.21475

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yao K, He L, Gan Y, Zeng Q, Dai Y, Tan J (2015) MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1. Diagn Pathol 10:146. doi:10.1186/s13000-015-0372-3

    Article  PubMed  PubMed Central  Google Scholar 

  43. Yu J, Peng H, Ruan Q, Fatima A, Getsios S, Lavker RM (2010) MicroRNA-205 promotes keratinocyte migration via the lipid phosphatase SHIP2. FASEB J 24:3950–3959. doi:10.1096/fj.10-157404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yu X, Li Z (2016) The role of miRNAs in cutaneous squamous cell carcinoma. J Cell Mol Med 20:3–9. doi:10.1111/jcmm.12649

    Article  CAS  PubMed  Google Scholar 

  45. Zhang L, Xiang P, Han X, Wu L, Li X, Xiong Z (2015) Decreased expression of microRNA-20a promotes tumor progression and predicts poor prognosis of cutaneous squamous cell carcinoma. Int J Clin Exp Pathol 8:11446–11451

    PubMed  PubMed Central  Google Scholar 

  46. Zhao W, Wang H, Han X, Ma J, Zhou Y, Chen Z, Zhou H, Xu H, Sun Z, Kong B, Fang H (2016) DeltaNp63alpha attenuates tumor aggressiveness by suppressing miR-205/ZEB1-mediated epithelial-mesenchymal transition in cervical squamous cell carcinoma. Tumour Biol. doi:10.1007/s13277-016-4921-5

    Google Scholar 

  47. Zheng N, Yang P, Wang Z, Zhou Q (2017) OncomicroRNAs-mediated tumorigenesis: implication in cancer diagnosis and targeted therapy. Curr Cancer Drug Targets 17(1):40–47

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. Michael McLeod for assistance in specimen collection, Shari Jackson for technical support and all members of Tomic-Canic laboratory.

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Authors and Affiliations

  1. Department of Dermatology and Cutaneous Surgery, Wound Healing and Regenerative Medicine Research Program, University of Miami Miller School of Medicine, 1600 N.W. 10th Avenue, RMSB, Room 2023-A, Miami, FL, 33136, USA

    Olivera Stojadinovic, Horacio Ramirez, Irena Pastar, Rivka Stone, Evangelos Badiavas & Marjana Tomic-Canic

  2. Department of Dermatology, UT Southwestern Medical Center, Dallas, TX, USA

    Katherine A. Gordon

  3. Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Sonal Choudhary, Evangelos Badiavas & Keyvan Nouri

  4. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA

    Marjana Tomic-Canic

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  1. Olivera Stojadinovic
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  2. Horacio Ramirez
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  3. Irena Pastar
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Correspondence to Marjana Tomic-Canic.

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The authors declare no competing financial interests. This work is supported by the University of Miami SAC Award SAC 2013-19 (MTC).

This study has been approved by the University of Miami institutional ethics committee (IRB protocol # 20090614) and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants included in the study.

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Stojadinovic, O., Ramirez, H., Pastar, I. et al. MiR-21 and miR-205 are induced in invasive cutaneous squamous cell carcinomas. Arch Dermatol Res 309, 133–139 (2017). https://doi.org/10.1007/s00403-016-1705-0

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