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Role of microRNA let-7 and effect to HMGA2 in esophageal squamous cell carcinoma

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Abstract

To investigated the role of microRNA (miRNA) let-7 and its regulation on high mobility group A2 (HMGA2) protein expression in esophageal squamous cell carcinoma (ESCC). Let-7 expressions were detected in esophageal cancer cell line Eca109, and 45 paired of fresh ESCC and normal adjacent tissues (NAT) by real-time quantitative PCR (qRT–PCR). To evaluate the role of let-7 and HMGA2, cell proliferations were analyzed with synthetic let-7 mimics- or its inhibitor-transfected cells. Moreover, expressions of HMGA2 were performed by western blotting and further confirmed by 150 paired of formalin-fixed, paraffin-embeded (FFPE) ESCC and NAT by immunohistochemistry (IHC). In Eca109, when transfected with let-7 mimics, accumulation of let-7 was obviously suppressed cell proliferation with approximately 14%. Conversely, when Eca109 transfected with let-7 inhibitor, expression of let-7 was declined, which promoted cell proliferation with approximately 16%. Both of them had no effect on the level of HMGA2 mRNA. The transcription of let-7 inversely correlated with HMGA2 protein. Compared with the NAT, expression of let-7 was significantly lower in ESCC tissues (P < 0.05), and there was a significant correlation between low expression of let-7 and lymph node metastasis in ESCC (P < 0.05). Moreover, the protein expression of HMGA2 was significantly higher in ESCC compared with NAT (P < 0.05). However, mRNA expression of HMGA2 had no obvious significance between them. The present results demonstrated that let-7 and HMGA2 involved in ESCC carcinogenesis. Let-7 could inhibit cell proliferation and lower expressed in ESCC, and there was a correlation between let-7 lower expression and lymph node metastasis in ESCC patients. As well as, HMGA2 protein expression was significantly higher in ESCC than that in NAT, and HMGA2 may negatively regulated by let-7 at the post- transcriptional level in ESCC.

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References

  1. Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Siegel R, Xu JQ et al (2010) Cancer statistics, 2010. Ca Cancer J Clin 60:277–300

    Article  PubMed  Google Scholar 

  3. Wang N, Dong XJ, Zhou RM et al (2009) An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China. Mol Biol Rep 36:357–364

    Article  PubMed  CAS  Google Scholar 

  4. Li Y, Sun DL, Duan YN et al (2009) Association of functional polymorphisms in MMPs genes with gastric cardia adenocarcinoma and esophageal squamous cell carcinoma in high incidence region of North China. Mol Biol Rep 37:197–205

    Article  PubMed  CAS  Google Scholar 

  5. Sayed D, Hong C, Chen IY et al (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 100:416–424

    Article  PubMed  CAS  Google Scholar 

  6. Lieberman J (2009) Micromanaging- cancer. N Engl J Med 361:1500–1501

    Article  PubMed  CAS  Google Scholar 

  7. Ma WJ, Lv GD, Tuersun A et al (2011) Role of microRNA-21 and effect on PTEN in Kazakh’s esophageal squamous cell carcinoma. Mol Biol Rep 38:3253–3260

    Article  PubMed  CAS  Google Scholar 

  8. Li R, You N, Wang X et al (2010) MicroRNAs involved in neoplastic transformation of liver cancer stem cells. J Exp Clin Cancer Res 29:169

    Article  PubMed  Google Scholar 

  9. Lima RT, Busacca S, Almeida GM et al (2011) MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer 47:163–174

    Article  PubMed  CAS  Google Scholar 

  10. Lu Z, Liu M, Stribinskis V et al (2008) MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 27:4373–4379

    Article  PubMed  CAS  Google Scholar 

  11. Reinhart BJ, Slack FJ, Basson M et al (2000) The 21 nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906

    Article  PubMed  CAS  Google Scholar 

  12. Takamizawa J, Konishi H, Takahashi T et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  PubMed  CAS  Google Scholar 

  13. Zhang HH, Wang XJ et al (2007) Detection of let-7a microRNA by real-time PCR in gastric carcinoma. World J Gastroenterol 13:2883–2888

    Article  PubMed  CAS  Google Scholar 

  14. Akao K, Nakagawa Y, Naoe T (2006) Let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull 9:903–906

    Article  Google Scholar 

  15. Young ARJ, Narita M (2007) Oncogenic HMGA2: short or small? Genes Dev 21:1005–1009

    Article  PubMed  CAS  Google Scholar 

  16. Rahman MM, Qian ZR, Wang EL et al (2009) Frequent overexpression of HMGA1 and 2 in gastroenteropancreatic neuroendocrine tumors and its relationship to let-7 downregulation. Br J Cancer 100:501–510

    Article  PubMed  CAS  Google Scholar 

  17. Hebert C, Norris K, Scheper MA et al (2007) High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma. Mol Cancer 6:5

    Article  PubMed  Google Scholar 

  18. Lee YS, Dutta A (2007) The tumor suppressor microRNA Let-7 represses the HMGA2 oncogene. Genes Dev 21:1025–1030

    Article  PubMed  CAS  Google Scholar 

  19. Zhang YM (1988) The distribution of esophageal cancer in Xinjiang. Acta Acad Med Xinjiang 11:139–144

    Google Scholar 

  20. Feber A, Xi LQ, Luketich JD et al (2007) MicroRNA expression profiles of esophageal cancer. General Thorac Surg 55:255–260

    Article  Google Scholar 

  21. Rogalla P, Drechsler K, Kazmierczak B et al (1997) Expression of HMGI-C, a member of the high mobility group protein family, in a subset of breast cancers: relationship to histologic grade. Mol Carcinog 19:153–156

    Article  PubMed  CAS  Google Scholar 

  22. Sarhadi VK, Wikman H, Salmenkivi K et al (2006) Increased expression of high mobility group A proteins in lung cancer. J Pathol 209:206–212

    Article  PubMed  CAS  Google Scholar 

  23. Meyer B, Loeschke S, Schultze A et al (2007) HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog 46:503–511

    Article  PubMed  CAS  Google Scholar 

  24. Motoyama K, Inoue H, Nakamura Y et al (2008) Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 14:2334–2340

    Article  PubMed  CAS  Google Scholar 

  25. Miyazawa J, Mitoro A, Kawashiri S et al (2004) Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Cancer Res 64:2024–2029

    Article  PubMed  CAS  Google Scholar 

  26. Bagga S, Bracht J, Hunter S et al (2005) Regulation by Let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122:553–563

    Article  PubMed  CAS  Google Scholar 

  27. Lee YS, Kim HK, Chung S et al (2005) Depletion of human microRNA 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 280:16635–16641

    Article  PubMed  CAS  Google Scholar 

  28. Pillai RS, Bhattacharyya SN, Artus CG et al (2005) Inhibition of translational initiation by Let-7 microRNA in human cells. Science 309:1573–1576

    Article  PubMed  CAS  Google Scholar 

  29. Johnson SM, Grosshans H, Shingara J et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The project was supported by Natural Science Foundation of China (No. 30860097), Postgraduate Innovation Fund of Xinjiang Medical University (No.MC2010-1), Xinjiang Key Laboratory of Molecular Biology and Endemic Diseases Grant (No. XJDX 0208-2009-02, XJDX0208-2010-06), Supporting Xinjiang through Science and Techology (No. 201191157) and National Key Technology R&D Program in the 11th Five year Plan of China (No. 2008BAI52B03).

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Correspondence to Xiao-mei Lu.

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Liu, Q., Lv, Gd., Qin, X. et al. Role of microRNA let-7 and effect to HMGA2 in esophageal squamous cell carcinoma. Mol Biol Rep 39, 1239–1246 (2012). https://doi.org/10.1007/s11033-011-0854-7

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  • DOI: https://doi.org/10.1007/s11033-011-0854-7

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