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Altered miRNA Expression is Associated with Differentiation, Invasion, and Metastasis of Esophageal Squamous Cell Carcinoma (ESCC) in Patients from Huaian, China

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Abstract

Esophageal squamous cell carcinoma (ESCC) is the leading malignancy in Huaian, China. Recently, emerging studies have suggested that an aberrant microRNA (miRNA) expression signature exists in ESCC. However, there is discordant information available on specific miRNA expression in patients from different regions. In this study, we identified 12 miRNAs that are differentially expressed in patients with ESCC from Huaian, China. Among these miRNAs that displayed unique miRNA expression signatures, miR-1, miR-29c, miR-100, miR-133a, miR-133b, miR-143, miR-145, and miR-195 were downregulated, and miR-7, miR-21, miR-223, and miR-1246 were upregulated in cancerous tissue compared with the adjacent normal tissue. Bioinformatics analyses identified the major biological processes and signaling pathways that are targeted by these differentially expressed miRNAs. Accordingly, miR-29c, miR-100, miR-133a, and miR-133b were found to be involved in invasion and metastasis of ESCC, and miR-7 and miR-21 were found to be related to the differentiation of ESCC. Thus, our data present new evidence for the important roles of miRNAs in ESCC.

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References

  1. Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116(2), 281–297.

    Article  PubMed  CAS  Google Scholar 

  2. Lewis, B. P., Burge, C. B., & Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120(1), 15–20.

    Article  PubMed  CAS  Google Scholar 

  3. Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435(7043), 834–838.

    Article  PubMed  CAS  Google Scholar 

  4. Calin, G. A., & Croce, C. M. (2006). MicroRNA signatures in human cancers. Nature Reviews Cancer, 6(11), 857–866.

    Article  PubMed  CAS  Google Scholar 

  5. Kong, Y. W., Ferland-McCollough, D., Jackson, T. J., & Bushell, M. (2012). microRNAs in cancer management. The Lancet Oncology, 13(6), e249–e258.

    Article  PubMed  CAS  Google Scholar 

  6. Jia, X. Q., Cheng, H. Q., Qian, X., Bian, C. X., Shi, Z. M., Zhang, J. P., et al. (2012). Lentivirus-mediated overexpression of microRNA-199a inhibits cell proliferation of human hepatocellular carcinoma. Cell Biochemistry and Biophysics, 62(1), 237–244.

    Article  PubMed  CAS  Google Scholar 

  7. Calin, G. A., Sevignani, C., Dumitru, C. D., Hyslop, T., Noch, E., Yendamuri, S., et al. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proceedings of the National Academy of Sciences of the United States of America, 101(9), 2999–3004.

    Article  PubMed  CAS  Google Scholar 

  8. Ferlay, J., Shin, H. R., Bray, F., Forman, D., Mathers, C., & Parkin, D. M. (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127(12), 2893–2917.

    Article  CAS  Google Scholar 

  9. Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69–90.

    Article  Google Scholar 

  10. He, B., Yin, B., Wang, B., Xia, Z., Chen, C., & Tang, J. (2012). MicroRNAs in esophageal cancer (review). Molecular Medicine Reports, 6(3), 459–465.

    PubMed  CAS  Google Scholar 

  11. Smith, C. M., Watson, D. I., Michael, M. Z., & Hussey, D. J. (2010). MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma. World Journal of Gastroenterology, 16(5), 531–537.

    Article  PubMed  CAS  Google Scholar 

  12. Mathe, E. A., Nguyen, G. H., Bowman, E. D., Zhao, Y., Budhu, A., Schetter, A. J., et al. (2009). MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: Associations with survival. Clinical Cancer Research, 15(19), 6192–6200.

    Article  PubMed  CAS  Google Scholar 

  13. Feber, A., Xi, L., Luketich, J. D., Pennathur, A., Landreneau, R. J., Wu, M., et al. (2008). MicroRNA expression profiles of esophageal cancer. Journal of Thoracic and Cardiovascular Surgery, 135(2), 255–260.

    Article  PubMed  CAS  Google Scholar 

  14. Ogawa, R., Ishiguro, H., Kuwabara, Y., Kimura, M., Mitsui, A., Katada, T., et al. (2009). Expression profiling of micro-RNAs in human esophageal squamous cell carcinoma using RT-PCR. Medical Molecular Morphology, 42(2), 102–109.

    Article  PubMed  CAS  Google Scholar 

  15. Guo, Y., Chen, Z., Zhang, L., Zhou, F., Shi, S., Feng, X., et al. (2008). Distinctive microRNA profiles relating to patient survival in esophageal squamous cell carcinoma. Cancer Research, 68(1), 26–33.

    Article  PubMed  CAS  Google Scholar 

  16. Matsushima, K., Isomoto, H., Yamaguchi, N., Inoue, N., Machida, H., Nakayama, T., et al. (2011). MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. Journal of Translational Medicine, 9, 30.

    Article  PubMed  CAS  Google Scholar 

  17. Ke, L. (2002). Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970–90. International Journal of Cancer, 102(3), 271–274.

    Article  CAS  Google Scholar 

  18. Li, Q. W., Yuan, G. J., Du, Y. X., Pan, E. C., & He, Y. (2012). Investigation of epidemic and treatment status of esophageal cancer in Huai’an area. Chinese Clinical Oncology, 17(2), 142–145.

    Google Scholar 

  19. Wang, L. D., Zhou, F. Y., Li, X. M., Sun, L. D., Song, X., Jin, Y., et al. (2010). Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54. Nature Genetics, 42(9), 759–763.

    Article  PubMed  CAS  Google Scholar 

  20. Sun, G., Wang, S., Hu, X., Su, J., Huang, T., Yu, J., et al. (2007). Fumonisin B1 contamination of home-grown corn in high-risk areas for esophageal and liver cancer in China. Food Additives and Contaminants, 24(2), 181–185.

    Article  PubMed  CAS  Google Scholar 

  21. Zhu, Q., Hong, A., Sheng, N., Zhang, X., Matejko, A., Jun, K. Y., et al. (2007). Microparaflo biochip for nucleic acid and protein analysis. Methods in Molecular Biology, 382, 287–312.

    Article  PubMed  CAS  Google Scholar 

  22. Gao, X., Gulari, E., & Zhou, X. (2004). In situ synthesis of oligonucleotide microarrays. Biopolymers, 73(5), 579–596.

    Article  PubMed  CAS  Google Scholar 

  23. Bolstad, B. M., Irizarry, R. A., Astrand, M., & Speed, T. P. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics, 19(2), 185–193.

    Article  PubMed  CAS  Google Scholar 

  24. Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., et al. (2000). Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nature Genetics, 25(1), 25–29.

    Article  PubMed  CAS  Google Scholar 

  25. Dennis, G. J., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., et al. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biology, 4(5), P3.

    Article  PubMed  Google Scholar 

  26. Nagaraja, A. K., Creighton, C. J., Yu, Z., Zhu, H., Gunaratne, P. H., Reid, J. G., et al. (2010). A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Molecular Endocrinology, 24(2), 447–463.

    Article  PubMed  CAS  Google Scholar 

  27. Ambros, V. (2004). The functions of animal microRNAs. Nature, 431(7006), 350–355.

    Article  PubMed  CAS  Google Scholar 

  28. Wu, B. L., Xu, L. Y., Du, Z. P., Liao, L. D., Zhang, H. F., Huang, Q., et al. (2011). MiRNA profile in esophageal squamous cell carcinoma: Downregulation of miR-143 and miR-145. World Journal of Gastroenterology, 17(1), 79–88.

    Article  PubMed  CAS  Google Scholar 

  29. Hiyoshi, Y., Kamohara, H., Karashima, R., Sato, N., Imamura, Y., Nagai, Y., et al. (2009). MicroRNA-21 regulates the proliferation and invasion in esophageal squamous cell carcinoma. Clinical Cancer Research, 15(6), 1915–1922.

    Article  PubMed  CAS  Google Scholar 

  30. Chabalier, J., Mosser, J., & Burgun, A. (2007). A transversal approach to predict gene product networks from ontology-based similarity. BMC Bioinformatics, 8, 235.

    Article  PubMed  Google Scholar 

  31. Lioni, M., Noma, K., Snyder, A., Klein-Szanto, A., Diehl, J. A., Rustgi, A. K., et al. (2008). Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Molecular Cancer Therapeutics, 7(9), 2866–2875.

    Article  PubMed  CAS  Google Scholar 

  32. Naganuma, S., Whelan, K. A., Natsuizaka, M., Kagawa, S., Kinugasa, H., Chang, S., et al. (2012). Notch receptor inhibition reveals the importance of cyclin D1 and Wnt signaling in invasive esophageal squamous cell carcinoma. American journal of cancer research, 2(4), 459–475.

    PubMed  CAS  Google Scholar 

  33. Li, H., Gao, Q., Guo, L., & Lu, S. H. (2011). The PTEN/PI3K/Akt pathway regulates stem-like cells in primary esophageal carcinoma cells. Cancer Biology and Therapy, 11(11), 950–958.

    Article  PubMed  CAS  Google Scholar 

  34. Zhao, X., & Guan, J. L. (2011). Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis. Advanced Drug Delivery Reviews, 63(8), 610–615.

    Article  PubMed  CAS  Google Scholar 

  35. Schwock, J., Dhani, N., & Hedley, D. W. (2010). Targeting focal adhesion kinase signaling in tumor growth and metastasis. Expert Opinion on Therapeutic Targets, 14(1), 77–94.

    Article  PubMed  CAS  Google Scholar 

  36. Pass, H. I., Goparaju, C., Ivanov, S., Donington, J., Carbone, M., Hoshen, M., et al. (2010). hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma. Cancer Research, 70(5), 1916–1924.

    Article  PubMed  CAS  Google Scholar 

  37. Wu, Z. S., Wang, C. Q., Xiang, R., Liu, X., Ye, S., Yang, X. Q., et al. (2012). Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion. BMC Cancer, 12, 51.

    Article  PubMed  CAS  Google Scholar 

  38. Akcakaya, P., Ekelund, S., Kolosenko, I., Caramuta, S., Ozata, D. M., Xie, H., et al. (2011). miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer. International Journal of Oncology, 39(2), 311–318.

    PubMed  Google Scholar 

  39. Leite, K. R., Sousa-Canavez, J. M., Reis, S. T., Tomiyama, A. H., Camara-Lopes, L. H., Sanudo, A., et al. (2011). Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis. Urologic Oncology, 29(3), 265–269.

    Article  PubMed  CAS  Google Scholar 

  40. Prochnik, S. E., Rokhsar, D. S., & Aboobaker, A. A. (2007). Evidence for a microRNA expansion in the bilaterian ancestor. Development Genes and Evolution, 217(1), 73–77.

    Article  PubMed  CAS  Google Scholar 

  41. Christodoulou, F., Raible, F., Tomer, R., Simakov, O., Trachana, K., Klaus, S., et al. (2010). Ancient animal microRNAs and the evolution of tissue identity. Nature, 463(7284), 1084–1088.

    Article  PubMed  CAS  Google Scholar 

  42. Li, B. H., Zhou, J. S., Ye, F., Cheng, X. D., Zhou, C. Y., Lu, W. G., et al. (2011). Reduced miR-100 expression in cervical cancer and precursors and its carcinogenic effect through targeting PLK1 protein. European Journal of Cancer, 47(14), 2166–2174.

    Article  PubMed  CAS  Google Scholar 

  43. Shi, W., Alajez, N. M., Bastianutto, C., Hui, A. B., Mocanu, J. D., Ito, E., et al. (2010). Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer. International Journal of Cancer, 126(9), 2036–2048.

    CAS  Google Scholar 

  44. Henson, B. J., Bhattacharjee, S., O’Dee, D. M., Feingold, E., & Gollin, S. M. (2009). Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes, Chromosomes and Cancer, 48(7), 569–582.

    Article  PubMed  CAS  Google Scholar 

  45. Chou, Y. T., Lin, H. H., Lien, Y. C., Wang, Y. H., Hong, C. F., Kao, Y. R., et al. (2010). EGFR promotes lung tumorigenesis by activating miR-7 through a Ras/ERK/Myc pathway that targets the Ets2 transcriptional repressor ERF. Cancer Research, 70(21), 8822–8831.

    Article  PubMed  CAS  Google Scholar 

  46. Jung, H. M., Phillips, B. L., Patel, R. S., Cohen, D. M., Jakymiw, A., Kong, W. W., et al. (2012). Keratinization-associated miR-7 and miR-21 Regulate Tumor Suppressor Reversion-inducing Cysteine-rich Protein with Kazal Motifs (RECK) in Oral Cancer. Journal of Biological Chemistry, 287(35), 29261–29272.

    Article  PubMed  CAS  Google Scholar 

  47. Liu, M., Tang, Q., Qiu, M., Lang, N., Li, M., Zheng, Y., et al. (2011). miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells. FEBS Letters, 585(19), 2998–3005.

    Article  PubMed  CAS  Google Scholar 

  48. Selcuklu, S. D., Donoghue, M. T., & Spillane, C. (2009). miR-21 as a key regulator of oncogenic processes. Biochemical Society Transactions, 37(Pt 4), 918–925.

    Article  PubMed  CAS  Google Scholar 

  49. Zhu, Q., Wang, Z., Hu, Y., Li, J., Li, X., Zhou, L., et al. (2012). miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma. Oncology Reports, 27(5), 1660–1668.

    PubMed  CAS  Google Scholar 

  50. Zhang, Z., Li, Z., Gao, C., Chen, P., Chen, J., Liu, W., et al. (2008). miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Laboratory Investigation, 88(12), 1358–1366.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The Natural Science Foundation of Jiangsu Province China (BK2012666).

Conflict of interest

The authors declare that no conflict of interest exists in relation to the content of this article.

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Authors and Affiliations

  1. Department of Laboratory Medicine, the 82nd Hospital of the People’s Liberation Army, Huaian, 223001, China

    Hai Long Fu, De Ping Wu, Xiu Fang Wang, Lei Lei Song, Hui Xie & Ya Ping Zhao

  2. Department of Postgraduates, BengBu Medical College, Bengbu, 233030, China

    Hai Long Fu, Xiu Fang Wang & Ya Ping Zhao

  3. Department of Medical Oncology, the 82nd Hospital of the People’s Liberation Army, Huaian, 223001, China

    Jian Guo Wang, Xu Yang Wen, Hu Sheng Shan & Yun Xiang Du

  4. Department of General Surgery, the 82nd Hospital of the People’s Liberation Army, Huaian, 223001, China

    Feng Jiao

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  1. Hai Long Fu
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Correspondence to Yun Xiang Du or Ya Ping Zhao.

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Hai Long Fu, De Ping Wu contributed equally to this work.

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12013_2013_9554_MOESM5_ESM.tif

miR-1, miR-29c, miR-100, miR-133a, miR-133b, miR-143, miR-145, miR-195, miR-7, miR-21, miR-223, and miR-1246 expression levels in 34 patients with ESCC (TIFF 39 kb)

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Fu, H.L., Wu, D.P., Wang, X.F. et al. Altered miRNA Expression is Associated with Differentiation, Invasion, and Metastasis of Esophageal Squamous Cell Carcinoma (ESCC) in Patients from Huaian, China. Cell Biochem Biophys 67, 657–668 (2013). https://doi.org/10.1007/s12013-013-9554-3

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