Human Pathology
Volume 41, Issue 4 , Pages 493-502 , April 2010

Correlation of overexpression of HMGA1 and HMGA2 with poor tumor differentiation, invasion, and proliferation associated with let-7 down-regulation in retinoblastomas

  • Guoying Mu, MD, PhD

      Affiliations

    • Department of Ophthalmology, Jinan Central Hospital affiliated to Shandong University, No. 105, Jiefang Road, Jinan 250013, China
    • These authors contributed equally to this work.
    • ,
  • Han Liu

      Affiliations

    • Department of Clinical Medicine, Medical School of Shandong University, No. 44, Wenhuaxi Road, Jinan 250012, China
    • These authors contributed equally to this work.
    • ,
  • Fang Zhou, MD

      Affiliations

    • Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, China
    • ,
  • Xiaoyi Xu, MD

      Affiliations

    • Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, China
    • ,
  • Hua Jiang, MD, PhD

      Affiliations

    • Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, China
    • ,
  • Yan Wang, BA

      Affiliations

    • Department of Pathology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, China
    • ,
  • Yi Qu, MD, PhD

      Affiliations

    • Department of Ophthalmology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan 250012, China
    • Corresponding Author InformationCorresponding author.

Received 12 May 2009 ,Revised 11 August 2009 ,Accepted 14 August 2009.

References 

  1. Dyer MA, Rodriguez-Galindo C, Wilson MW. Use of preclinical models to improve treatment of retinoblastoma. PLoS Med. 2005;e332:2
  2. Corson TW, Gallie BL. One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes Chromosomes Cancer. 2007;46:617–634
  3. Johnson KR, Lehn DA, Reeves R. Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol. 1989;9:2114–2123
  4. Reeves R, Nissen MS. The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem. 1990;265:8573–8582
  5. Thanos D, Maniatis T. The high mobility group protein HMG I (Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992;71:777–789
  6. Thanos D, Du W, Maniatis T. The high mobility group protein HMG I (Y) is an essential structural component of a virus-inducible enhancer complex. Cold Spring Harb Symp Quant Biol. 1993;58:73–81
  7. Zhou X, Benson KF, Ashar HR, Chada K. Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature. 1995;376:771–774
  8. Chiappetta G, Avantaggiato V, Visconti R, et al. High level expression of the HMGI (Y) gene during embryonic development. Oncogene. 1996;13:2439–2446
  9. Sgarra R, Rustighi A, Tessari MA, et al. Nuclear phosphoproteins HMGA and their relationship with chromatin structure and cancer. FEBS Lett. 2004;574:1–8
  10. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7:899–910
  11. Caldas C, Brenton JD. Sizing up miRNAs as cancer genes. Nat Med. 2005;11:712–714
  12. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–269
  13. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403:901–906
  14. Pasquinelli AE, Reinhart BJ, Slack F, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000;408:86–89
  15. Lee YS, Kim HK, Chung S, Kim KS, Dutta A. Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J Biol Chem. 2005;280:16635–16641
  16. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007;315:1576–1579
  17. Wang T, Zhang X, Obijuru L, et al. A micro-RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas. Genes Chromosomes Cancer. 2007;46:336–347
  18. Motoyama K, Inoue H, Nakamura Y, Uetake H, Sugihara K, Mori M. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res. 2008;14:2334–2340
  19. Shell S, Park SM, Radjabi AR, et al. Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci U S A. 2007;104:11400–11405
  20. Qian ZR, Asa SL, Siomi H, et al. Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. Mod Pathol. 2009;22:431–441
  21. Rahman MM, Qian ZR, Wang EL, et al. Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumours and its relationship to let-7 downregulation. Br J Cancer. 2009;100:501–510
  22. Ryan DG, Oliveira-Fernandes M, Lavker RM. MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol Vis. 2006;12:1175–1184
  23. Arora A, McKay GJ, Simpson DA. Prediction and verification of miRNA expression in human and rat retinas. Invest Ophthalmol Vis Sci. 2007;48:3962–3967
  24. Szafranska AE, Davison TS, Shingara J, et al. Accurate molecular characterization of formalin-fixed, paraffin-embedded tissues by microRNA expression profiling. J Mol Diagn. 2008;10:415–423
  25. Zhang X, Chen J, Radcliffe T, Lebrun DP, Tron VA, Feilotter H. An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn. 2008;10:513–519
  26. Reeves R. Molecular biology of HMGA proteins: hubs of nuclear function. Gene. 2001;277:63–81
  27. Yang J, Zhao JJ, Zhu Y, Xiong W, Lin JY, Ma X. Identification of candidate cancer genes involved in human retinoblastoma by data mining. Childs Nerv Syst. 2008;24:893–900
  28. Chau KY, Manfioletti G, Cheung-Chau KW, et al. Derepression of HMGA2 gene expression in retinoblastoma is associated with cell proliferation. Mol Med. 2003;9:154–165
  29. Sawai J, Nakazato Y, Yamane Y, Kimura N, Kishi S. Immunohistochemical localization of human pineal tissue antigens in normal retina and retinoblastomas. Neuropathology. 2003;23:119–128
  30. Finger PT, Harbour JW, Karcioglu ZA. Risk factors for metastasis in retinoblastoma. Surv Ophthalmol. 2002;47:1–16
  31. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322
  32. Kim CJ, Chi JG, Choi HS, et al. Proliferation not apoptosis as a prognostic indicator in retinoblastoma. Virchows Arch. 1999;434:301–305
  33. Liau SS, Jazag A, Whang EE. HMGA1 is a determinant of cellular invasiveness and in vivo metastatic potential in pancreatic adenocarcinoma. Cancer Res. 2006;66:11613–11622
  34. Pentimalli F, Dentice M, Fedele M, et al. Suppression of HMGA2 protein synthesis could be a tool for the therapy of well differentiated liposarcomas overexpressing HMGA2. Cancer Res. 2003;63:7423–7427
  35. Pierantoni GM, Rinaldo C, Esposito F, Mottolese M, Soddu S, Fusco A. High Mobility Group A1 (HMGA1) proteins interact with p53 and inhibit its apoptotic activity. Cell Death Differ. 2006;13:1554–1563
  36. Laurie NA, Donovan SL, Shih CS, et al. Inactivation of the p53 pathway in retinoblastoma. Nature. 2006;444:61–66
  37. Johnson CD, Esquela-Kerscher A, Stefani G, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713–7722
  38. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005;120:635–647
  39. Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64:3753–3756
  40. Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–7070
  41. Scott IU, Murray TG, Toledano S, O'Brien JM. New retinoblastoma tumors in children undergoing systemic chemotherapy. Arch Ophthalmol. 1998;116:1685–1686
  42. Scala S, Portella G, Fedele M, Chiappetta G, Fusco A. Adenovirus-mediated suppression of HMGI (Y) protein synthesis as potential therapy of human malignant neoplasias. Proc Natl Acad Sci U S A. 2000;97:4256–4261

☆ This research was supported in part by Department of Science and Technology of Shandong Province of China (Y2008C89, 2007GG30002026 and 2009GG10002016).

☆☆ The authors have no proprietary or financial interest in any material or device mentioned.

PII: S0046-8177(09)00335-9

doi: 10.1016/j.humpath.2009.08.022

Human Pathology
Volume 41, Issue 4 , Pages 493-502 , April 2010

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