BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer

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• 作者：Tao Hu (1)
  Yu-Run Lu (1)
  
  1. Sichuan Provincial People鈥檚 Hospital ; No. 32 ; Section 2 ; 1st Ring Road (West) ; Chengdu City ; 610072 ; China
  
• 关键词：BCYRN1 (brain cytoplasmic RNA 1) ; lncRNA (long non ; coding RNA) ; c ; MYC ; Metastasis ; NSCLC (non ; small ; cell lung cancer)
• 刊名：Cancer Cell International
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：1
• 全文大小：1,854 KB
• 参考文献：1. Stewart, BW, Wild, C (2014) World cancer report 2014: World Health Organization.
  2. Siegel, R, Ma, J, Zou, Z, Jemal, A (2014) Cancer statistics, 2014. CA Cancer J Clin 64: pp. 9-29 CrossRef
  3. Kawabata, S, Chiang, C-T, Memmott, RM, Komiya, T, Gills, JJ, Dennis, PA (2014) Rapamycin decreases expression of thymidylate synthase and enhances the response to pemetrexed in preclinical studies and a Phase I/II clinical study of subjects with non-small cell lung cancer. Cancer Res 74: pp. 2927
  4. Rapp, UR, Korn, C, Ceteci, F, Karreman, C, Luetkenhaus, K, Serafin, V (2009) MYC is a metastasis gene for non-small-cell lung cancer. PLoS One 4: pp. e6029 CrossRef
  5. Bu D, Yu K, Sun S, Xie C, Skogerb酶 G, Miao R, et al. NONCODE v3.0: integrative annotation of long noncoding RNAs. Nucleic Acids Research 2012 Jan;40(Database issue):D210-5. doi: 10.1093/nar/gkr1175.
  6. Tsai, M-C, Spitale, RC, Chang, HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71: pp. 3-7 CrossRef
  7. Xu, C, Yang, M, Tian, J, Wang, X, Li, Z (2011) MALAT-1: a long non-coding RNA and its important 3鈥瞖nd functional motif in colorectal cancer metastasis. Int J Oncol 39: pp. 169-75
  8. Gupta, RA, Shah, N, Wang, KC, Kim, J, Horlings, HM, Wong, DJ (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464: pp. 1071-6 CrossRef
  9. Schmidt, LH, Spieker, T, Koschmieder, S, Humberg, J, Jungen, D, Bulk, E (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol 6: pp. 1984-92 CrossRef
  10. Tano, K, Mizuno, R, Okada, T, Rakwal, R, Shibato, J, Masuo, Y (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett 584: pp. 4575-80 CrossRef
  11. Chen, W, B枚cker, W, Brosius, J, Tiedge, H (1997) Expression of neural BC200 RNA in human tumours. J Pathol 183: pp. 345-51 CrossRef
  12. Redvers, RP, Anderson, RL (2000) Long Non-Coding RNA: Agent Provocateur in Breast Cancer Metastasis.
  13. Iacoangeli, A, Lin, Y, Morley, EJ, Muslimov, IA, Bianchi, R, Reilly, J (2004) BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis 25: pp. 2125-33 CrossRef
  14. Han, J-Y, Kim, HS, Lee, SH, Park, WS, Lee, JY, Yoo, NJ (2003) Immunohistochemical expression of integrins and extracellular matrix proteins in non-small cell lung cancer: correlation with lymph node metastasis. Lung Cancer 41: pp. 65-70 CrossRef
  15. Hofmann, H-S, Hansen, G, Richter, G, Taege, C, Simm, A, Silber, R-E (2005) Matrix metalloproteinase-12 expression correlates with local recurrence and metastatic disease in non鈥搒mall cell lung cancer patients. Clin Cancer Res 11: pp. 1086-92
  16. Zhuang, D, Mannava, S, Grachtchouk, V, Tang, W, Patil, S, Wawrzyniak, J (2008) C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene 27: pp. 6623-34 CrossRef
  17. Pello, OM, De Pizzol, M, Mirolo, M, Soucek, L, Zammataro, L, Amabile, A (2012) Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood 119: pp. 411-21 CrossRef
  18. Schomber, T, Kalberer, CP, Wodnar-Filipowicz, A, Skoda, RC (2004) Gene silencing by lentivirus-mediated delivery of siRNA in human CD34+ cells. Blood 103: pp. 4511-3 CrossRef
  19. Jiang, L, Huang, Q, Zhang, S, Zhang, Q, Chang, J, Qiu, X (2010) Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells. BMC Cancer 10: pp. 318 CrossRef
  20. Morgia, G, Falsaperla, M, Malaponte, G, Madonia, M, Indelicato, M, Travali, S (2005) Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-2, MMP-9) markers of prostate cancer. Urol Res 33: pp. 44-50 CrossRef
  21. Singla AK, Thirukkumaran C, Dixit R, Wu W. Genomic Landscape of Cancer Metastasis. In: Next Generation Sequencing in Cancer Research. Springer; 2013: 75鈥?0.
  22. Dang CV, O鈥橠onnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-Myc target gene network. In: Semin Cancer Biol: 2006: Elsevier; 2006: 253鈥?64.
  23. He, T-C, Sparks, AB, Rago, C, Hermeking, H, Zawel, L, Da Costa, LT (1998) Identification of c-MYC as a target of the APC pathway. Science 281: pp. 1509-12 CrossRef
  24. Wang, J, Kobayashi, T, Floc鈥檋, N, Kinkade, CW, Aytes, A, Dankort, D (2012) B-Raf activation cooperates with PTEN loss to drive c-Myc expression in advanced prostate cancer. Cancer Res 72: pp. 4765-76 CrossRef
  25. Yu, T, Wu, Y, Helman, JI, Wen, Y, Wang, C, Li, L (2011) CXCR4 promotes oral squamous cell carcinoma migration and invasion through inducing expression of MMP-9 and MMP-13 via the ERK signaling pathway. Mol Cancer Res 9: pp. 161-72 CrossRef
  26. Nabeshima, K, Inoue, T, Shimao, Y, Sameshima, T (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52: pp. 255-64 CrossRef
  27. Friedl, P, Wolf, K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3: pp. 362-74 CrossRef
  28. Bourguignon, LY, Gunja-Smith, Z, Iida, N, Zhu, H, Young, L, Muller, WJ (1998) CD44v3,8鈥?0 Is Involved in Cytoskeleton-Mediated Tumor Cell Migration and Matrix Metalloproteinase (MMP-9) Association in Metastatic Breast Cancer Cells. J Cell Physiol 176: pp. 206-15 CrossRef
  29. Polette, M, Nawrocki-Raby, B, Gilles, C, Clavel, C, Birembaut, P (2004) Tumour invasion and matrix metalloproteinases. Crit Rev Oncol Hematol 49: pp. 179-86 CrossRef
  30. Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. In: Seminars in cancer biology: 2000: Elsevier; 2000: 415鈥?33.
  31. Ghosh, S, Basu, M, Roy, SS (2012) ETS-1 protein regulates vascular endothelial growth factor-induced matrix metalloproteinase-9 and matrix metalloproteinase-13 expression in human ovarian carcinoma cell line SKOV-3. J Biol Chem 287: pp. 15001-15 CrossRef
  
• 刊物主题：Cancer Research; Cell Biology;
• 出版者：BioMed Central
• ISSN：1475-2867

文摘

Background Long non-coding RNAs (lncRNAs) are increasingly implicated in the regulation of the progression of malignancy. Aim To clarify the relations among BCYRN1 (brain cytoplasmic RNA 1, a long non-coding RNA), c-MYC and cell metastasis of non-small-cell lung cancer (NSCLC). Methods Real-time PCR was used to measure expression of BCYRN1 in NSCLC. Knockdown and overexpression of c-MYC were respectively performed using shRNA and lentivirus to investigate its effect on BCYRN1 expression. BCYRN1 was respectively knockdown and overexpressed by siRNA and BCYRN1 mimics to investigate its role in regulating cell metastasis in vitro. ChIP (chromatin immunoprecipitation) assay was performed to confirm the binding of c-MYC to the promoter of BCYRN1. Expression levels of matrix metalloproteinases (MMP9 and MMP13) were determined using real-time PCR and Western blotting. Results BCYRN1 is upregulated and targeted by c-MYC in NSCLC, leading to the increase of cell motility and invasiveness. RNA interference and lentivirus infection showed a positive correlation between the expressions of c-MYC and BCYRN1. ChIP assay confirmed the binding of c-MYC to the promoter region of BCYRN1 gene. In-vitro cell metastasis experiments demonstrated that BCYRN1 was necessary in the c-MYC-regulated cell migration and invasion. The mRNA and protein expression levels of MMP9 and MMP13 descended with the decreasing BCYRN1 level and ascended with the upregulation of BCYRN1. Conclusion These findings uncover a regulatory mechanism in NSCLC cells involving the metastasis-promoting lncRNA BCYRN1 that improves expressions of the key metastasis-supporting proteins MMP9 and MMP13.