DOI QR코드

DOI QR Code

Long Noncoding RNA Expression Profiling Reveals Upregulation of Uroplakin 1A and Uroplakin 1A Antisense RNA 1 under Hypoxic Conditions in Lung Cancer Cells

  • Byun, Yuree (Graduate School of Biotechnology, Kyung Hee University) ;
  • Choi, Young-Chul (Graduate School of Biotechnology, Kyung Hee University) ;
  • Jeong, Yongsu (Graduate School of Biotechnology, Kyung Hee University) ;
  • Yoon, Jaeseung (Graduate School of Biotechnology, Kyung Hee University) ;
  • Baek, Kwanghee (Graduate School of Biotechnology, Kyung Hee University)
  • 투고 : 2020.05.30
  • 심사 : 2020.11.03
  • 발행 : 2020.12.31

초록

Hypoxia plays important roles in cancer progression by inducing angiogenesis, metastasis, and drug resistance. However, the effects of hypoxia on long noncoding RNA (lncRNA) expression have not been clarified. Herein, we evaluated alterations in lncRNA expression in lung cancer cells under hypoxic conditions using lncRNA microarray analyses. Among 40,173 lncRNAs, 211 and 113 lncRNAs were up- and downregulated, respectively, in both A549 and NCI-H460 cells. Uroplakin 1A (UPK1A) and UPK1A-antisense RNA 1 (AS1), which showed the highest upregulation under hypoxic conditions, were selected to investigate the effects of UPK1A-AS1 on the expression of UPK1A and the mechanisms of hypoxia-inducible expression. Following transfection of cells with small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α), the hypoxia-induced expression of UPK1A and UPK1A-AS1 was significantly reduced, indicating that HIF-1α played important roles in the hypoxia-induced expression of these targets. After transfection of cells with UPK1A siRNA, UPK1A and UPK1A-AS1 levels were reduced. Moreover, transfection of cells with UPK1A-AS1 siRNA downregulated both UPK1A-AS1 and UPK1A. RNase protection assays demonstrated that UPK1A and UPK1A-AS1 formed a duplex; thus, transfection with UPK1A-AS1 siRNA decreased the RNA stability of UPK1A. Overall, these results indicated that UPK1A and UPK1A-AS1 expression increased under hypoxic conditions in a HIF-1α-dependent manner and that formation of a UPK1A/UPK1A-AS1 duplex affected RNA stability, enabling each molecule to regulate the expression of the other.

키워드

과제정보

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (grant No. 2015R1D1A1A01057433).

참고문헌

  1. Autuoro, J.M., Pirnie, S.P., and Carmichael, G.G. (2014). Long noncoding RNAs in imprinting and X chromosome inactivation. Biomolecules 4, 76-100. https://doi.org/10.3390/biom4010076
  2. Bach, D.H. and Lee, S.K. (2018). Long noncoding RNAs in cancer cells. Cancer Lett. 419, 152-166. https://doi.org/10.1016/j.canlet.2018.01.053
  3. Cabili, M.N., Trapnell, C., Goff, L., Koziol, M., Tazon-Vega, B., Regev, A., and Rinn, J.L. (2011). Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25, 1915-1927. https://doi.org/10.1101/gad.17446611
  4. Chang, Y.N., Zhang, K., Hu, Z.M., Qi, H.X., Shi, Z.M., Han, X.H., Han, Y.W., and Hong, W. (2016). Hypoxia-regulated lncRNAs in cancer. Gene 575, 1-8. https://doi.org/10.1016/j.gene.2015.08.049
  5. Chatterjee, A., Stockwell, P.A., Ahn, A., Rodger, E.J., Leichter, A.L., and Eccles, M.R. (2017). Genome-wide methylation sequencing of paired primary and metastatic cell lines identifies common DNA methylation changes and a role for EBF3 as a candidate epigenetic driver of melanoma metastasis. Oncotarget 8, 6085-6101. https://doi.org/10.18632/oncotarget.14042
  6. Du, F., Guo, T., and Cao, C. (2020). Restoration of UPK1A-AS1 expression suppresses cell proliferation, migration, and invasion in esophageal squamous cell carcinoma cells partially by sponging microRNA-1248. Cancer Manag. Res. 12, 2653-2662. https://doi.org/10.2147/CMAR.S239418
  7. Elvidge, G.P., Glenny, L., Appelhoff, R.J., Ratcliffe, P.J., Ragoussis, J., and Gleadle, J.M. (2006). Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways. J. Biol. Chem. 281, 15215-15226. https://doi.org/10.1074/jbc.M511408200
  8. Faghihi, M.A., Modarresi, F., Khalil, A.M., Wood, D.E., Sahagan, B.G., Morgan, T.E., Finch, C.E., St Laurent, G., 3rd, Kenny, P.J., and Wahlestedt, C. (2008). Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of beta-secretase. Nat. Med. 14, 723-730. https://doi.org/10.1038/nm1784
  9. Fiedler, J., Breckwoldt, K., Remmele, C.W., Hartmann, D., Dittrich, M., Pfanne, A., Just, A., Xiao, K., Kunz, M., Müller, T., et al. (2015). Development of long noncoding RNA-based strategies to modulate tissue vascularization. J. Am. Coll. Cardiol. 66, 2005-2015. https://doi.org/10.1016/j.jacc.2015.07.081
  10. Gomez-Maldonado, L., Tiana, M., Roche, O., Prado-Cabrero, A., Jensen, L., Fernandez-Barral, A., Guijarro-Munoz, I., Favaro, E., Moreno-Bueno, G., Sanz, L., et al. (2015). EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination. Oncogene 34, 2609-2620. https://doi.org/10.1038/onc.2014.200
  11. Guillaumet-Adkins, A., Richter, J., Odero, M.D., Sandoval, J., Agirre, X., Catala, A., Esteller, M., Prosper, F., Calasanz, M.J., Buno, I., et al. (2014). Hypermethylation of the alternative AWT1 promoter in hematological malignancies is a highly specific marker for acute myeloid leukemias despite high expression levels. J. Hematol. Oncol. 7, 4. https://doi.org/10.1186/1756-8722-7-4
  12. Guilleret, I., Yan, P., Grange, F., Braunschweig, R., Bosman, F.T., and Benhattar, J. (2002). Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity. Int. J. Cancer 101, 335-341. https://doi.org/10.1002/ijc.10593
  13. Hall, G.D., Weeks, R.J., Olsburgh, J., Southgate, J., Knowles, M.A., Selby, P.J., and Chester, J.D. (2005). Transcriptional control of the human urothelialspecific gene, uroplakin Ia. Biochim. Biophys. Acta 1729, 126-134. https://doi.org/10.1016/j.bbaexp.2005.04.004
  14. He, Y., Kong, F., Du, H., and Wu, M. (2014). Decreased expression of uroplakin Ia is associated with colorectal cancer progression and poor survival of patients. Int. J. Clin. Exp. Pathol. 7, 5031-5037.
  15. Hong, S.S., Lee, H., and Kim, K.W. (2004). HIF-1alpha: a valid therapeutic target for tumor therapy. Cancer Res. Treat. 36, 343-353. https://doi.org/10.4143/crt.2004.36.6.343
  16. Hu, S., Wang, X., and Shan, G. (2016). Insertion of an Alu element in a lncRNA leads to primate-specific modulation of alternative splicing. Nat. Struct. Mol. Biol. 23, 1011-1019. https://doi.org/10.1038/nsmb.3302
  17. Hu, Y., Liu, J., and Huang, H. (2013). Recent agents targeting HIF-1α for cancer therapy. J. Cell. Biochem. 114, 498-509. https://doi.org/10.1002/jcb.24390
  18. Huang, B., Song, J.H., Cheng, Y., Abraham, J.M., Ibrahim, S., Sun, Z., Ke, X., and Meltzer, S.J. (2016). Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression. Oncogene 35, 4927-4936. https://doi.org/10.1038/onc.2016.25
  19. Iyer, M.K., Niknafs, Y.S., Malik, R., Singhal, U., Sahu, A., Hosono, Y., Barrette, T.R., Prensner, J.R., Evans, J.R., Zhao, S., et al. (2015). The landscape of long noncoding RNAs in the human transcriptome. Nat. Genet. 47, 199-208. https://doi.org/10.1038/ng.3192
  20. Jiang, B.H., Rue, E., Wang, G.L., Roe, R., and Semenza, G.L. (1996). Dimerization, DNA binding, and transactivation properties of hypoxiainducible factor 1. J. Biol. Chem. 271, 17771-17778. https://doi.org/10.1074/jbc.271.30.17771
  21. Jones, P.A. and Takai, D. (2001). The role of DNA methylation in mammalian epigenetics. Science 293, 1068-1070. https://doi.org/10.1126/science.1063852
  22. Kanduri, C. (2016). Long noncoding RNAs: lessons from genomic imprinting. Biochim. Biophys. Acta 1859, 102-111. https://doi.org/10.1016/j.bbagrm.2015.05.006
  23. Ke, Q. and Costa, M. (2006). Hypoxia-inducible factor-1 (HIF-1). Mol. Pharmacol. 70, 1469-1480. https://doi.org/10.1124/mol.106.027029
  24. Kim, S., Lee, U.J., Kim, M.N., Lee, E.J., Kim, J.Y., Lee, M.Y., Choung, S., Kim, Y.J., and Choi, Y.C. (2008). MicroRNA miR-199a* regulates the MET protooncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J. Biol. Chem. 283, 18158-18166. https://doi.org/10.1074/jbc.M800186200
  25. Kimura, T., Jiang, S., Nishizawa, M., Yoshigai, E., Hashimoto, I., Nishikawa, M., Okumura, T., and Yamada, H. (2013). Stabilization of human interferon-α1 mRNA by its antisense RNA. Cell. Mol. Life Sci. 70, 1451-1467. https://doi.org/10.1007/s00018-012-1216-x
  26. Klose, R.J. and Bird, A.P. (2006). Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 31, 89-97. https://doi.org/10.1016/j.tibs.2005.12.008
  27. Kong, K.L., Kwong, D.L., Fu, L., Chan, T.H., Chen, L., Liu, H., Li, Y., Zhu, Y.H., Bi, J., Qin, Y.R., et al. (2010). Characterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinoma. Cancer Res. 70, 8832-8841. https://doi.org/10.1158/0008-5472.CAN-10-0779
  28. Kulshreshtha, R., Ferracin, M., Wojcik, S.E., Garzon, R., Alder, H., Agosto-Perez, F.J., Davuluri, R., Liu, C.G., Croce, C.M., Negrini, M., et al. (2007). A microRNA signature of hypoxia. Mol. Cell. Biol. 27, 1859-1867. https://doi.org/10.1128/MCB.01395-06
  29. Lauer, V., Grampp, S., Platt, J., Lafleur, V., Lombardi, O., Choudhry, H., Kranz, F., Hartmann, A., Wullich, B., Yamamoto, A., et al. (2020). Hypoxia drives glucose transporter 3 expression through hypoxia-inducible transcription factor (HIF)-mediated induction of the long noncoding RNA NICI. J. Biol. Chem. 295, 4065-4078. https://doi.org/10.1074/jbc.ra119.009827
  30. Lee, D.D., Leao, R., Komosa, M., Gallo, M., Zhang, C.H., Lipman, T., Remke, M., Heidari, A., Nunes, N.M., Apolonio, J.D., et al. (2019). DNA hypermethylation within TERT promoter upregulates TERT expression in cancer. J. Clin. Invest. 129, 223-229. https://doi.org/10.1172/JCI121303
  31. Lelli, A., Nolan, K.A., Santambrogio, S., Gonçalves, A.F., Schonenberger, M.J., Guinot, A., Frew, I.J., Marti, H.H., Hoogewijs, D., and Wenger, R.H. (2015). Induction of long noncoding RNA MALAT1 in hypoxic mice. Hypoxia (Auckl.) 3, 45-52. https://doi.org/10.2147/hp.s90555
  32. Li, T., Xiao, Y., and Huang, T. (2018). HIF-1α-induced upregulation of lncRNA UCA1 promotes cell growth in osteosarcoma by inactivating the PTEN/AKT signaling pathway. Oncol. Rep. 39, 1072-1080.
  33. Lin, J., Zhang, X., Xue, C., Zhang, H., Shashaty, M.G., Gosai, S.J., Meyer, N., Grazioli, A., Hinkle, C., and Caughey, J. (2015). The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury. Am. J. Physiol. Renal Physiol. 309, F901-F913. https://doi.org/10.1152/ajprenal.00290.2015
  34. Lubelsky, Y. and Ulitsky, I. (2018). Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 555, 107-111. https://doi.org/10.1038/nature25757
  35. Maxwell, P.H., Wiesener, M.S., Chang, G.W., Clifford, S.C., Vaux, E.C., Cockman, M.E., Wykoff, C.C., Pugh, C.W., Maher, E.R., and Ratcliffe, P.J. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271-275. https://doi.org/10.1038/20459
  36. Mercer, T.R., Dinger, M.E., and Mattick, J.S. (2009). Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 10, 155-159. https://doi.org/10.1038/nrg2521
  37. Mimura, I., Hirakawa, Y., Kanki, Y., Kushida, N., Nakaki, R., Suzuki, Y., Tanaka, T., Aburatani, H., and Nangaku, M. (2017). Novel lnc RNA regulated by HIF-1 inhibits apoptotic cell death in the renal tubular epithelial cells under hypoxia. Physiol. Rep. 5, e13203. https://doi.org/10.14814/phy2.13203
  38. Nabilsi, N.H., Broaddus, R.R., and Loose, D.S. (2009). DNA methylation inhibits p53-mediated survivin repression. Oncogene 28, 2046-2050. https://doi.org/10.1038/onc.2009.62
  39. Penny, G.D., Kay, G.F., Sheardown, S.A., Rastan, S., and Brockdorff, N. (1996). Requirement for Xist in X chromosome inactivation. Nature 379, 131-137. https://doi.org/10.1038/379131a0
  40. Pollex, T. and Heard, E. (2012). Recent advances in X-chromosome inactivation research. Curr. Opin. Cell Biol. 24, 825-832. https://doi.org/10.1016/j.ceb.2012.10.007
  41. Scheuermann, J.C. and Boyer, L.A. (2013). Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease. EMBO J. 32, 1805-1816. https://doi.org/10.1038/emboj.2013.134
  42. Schmitt, A.M. and Chang, H.Y. (2016). Long noncoding RNAs in cancer pathways. Cancer Cell. 29, 452-463. https://doi.org/10.1016/j.ccell.2016.03.010
  43. Schonrock, N., Harvey, R.P., and Mattick, J.S. (2012). Long noncoding RNAs in cardiac development and pathophysiology. Circ. Res. 111, 1349-1362. https://doi.org/10.1161/CIRCRESAHA.112.268953
  44. Semenza, G.L. (2003). Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3, 721-732. https://doi.org/10.1038/nrc1187
  45. Shih, J.W. and Kung, H.J. (2017). Long non-coding RNA and tumor hypoxia: new players ushered toward an old arena. J. Biomed. Sci. 24, 53. https://doi.org/10.1186/s12929-017-0358-4
  46. Smith, J., Sen, S., Weeks, R.J., Eccles, M.R., and Chatterjee, A. (2020). Promoter DNA hypermethylation and paradoxical gene activation. Trends Cancer 6, 392-406. https://doi.org/10.1016/j.trecan.2020.02.007
  47. Song, Y., Wang, H., Zou, X.J., Zhang, Y.X., Guo, Z.Q., Liu, L., Wu, D.H., and Zhang, D.Y. (2020). Reciprocal regulation of HIF-1α and Uroplakin 1A promotes glycolysis and proliferation in Hepatocellular Carcinoma. J. Cancer 11, 6737-6747. https://doi.org/10.7150/jca.48132
  48. Su, W., Xu, M., Chen, X., Chen, N., Gong, J., Nie, L., Li, L., Li, X., Zhang, M., and Zhou, Q. (2017). Long noncoding RNA ZEB1-AS1 epigenetically regulates the expressions of ZEB1 and downstream molecules in prostate cancer. Mol. Cancer 16, 142. https://doi.org/10.1186/s12943-017-0711-y
  49. Sun, J., Wang, X., Fu, C., Wang, X., Zou, J., Hua, H., and Bi, Z. (2016). Long noncoding RNA FGFR3-AS1 promotes osteosarcoma growth through regulating its natural antisense transcript FGFR3. Mol. Biol. Rep. 43, 427-436. https://doi.org/10.1007/s11033-016-3975-1
  50. Tang, Y., Cheung, B.B., Atmadibrata, B., Marshall, G.M., Dinger, M.E., Liu, P.Y., and Liu, T. (2017). The regulatory role of long noncoding RNAs in cancer. Cancer Lett. 391, 12-19. https://doi.org/10.1016/j.canlet.2017.01.010
  51. Tee, A.E., Liu, B., Song, R., Li, J., Pasquier, E., Cheung, B.B., Jiang, C., Marshall, G.M., Haber, M., Norris, M.D., et al. (2016). The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating proangiogenic gene expression. Oncotarget 7, 8663-8675. https://doi.org/10.18632/oncotarget.6675
  52. Voellenkle, C., Garcia-Manteiga, J.M., Pedrotti, S., Perfetti, A., De Toma, I., Da Silva, D., Maimone, B., Greco, S., Fasanaro, P., Creo, P., et al. (2016). Implication of long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing. Sci. Rep. 6, 24141. https://doi.org/10.1038/srep24141
  53. Wang, Y., Liu, X., Zhang, H., Sun, L., Zhou, Y., Jin, H., Zhang, H., Zhang, H., Liu, J., Guo, H., et al. (2014). Hypoxia-inducible lncRNA-AK058003 promotes gastric cancer metastasis by targeting γ-synuclein. Neoplasia 16, 1094-1106. https://doi.org/10.1016/j.neo.2014.10.008
  54. Wu, X.R., Kong, X.P., Pellicer, A., Kreibich, G., and Sun, T.T. (2009). Uroplakins in urothelial biology, function, and disease. Kidney Int. 75, 1153-1165. https://doi.org/10.1038/ki.2009.73
  55. Xue, M., Li, X., Li, Z., and Chen, W. (2014). Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1α-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 35, 6901-6912. https://doi.org/10.1007/s13277-014-1925-x
  56. Yap, K.L., Li, S., Munoz-Cabello, A.M., Raguz, S., Zeng, L., Mujtaba, S., Gil, J., Walsh, M.J., and Zhou, M.M. (2010). Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol. Cell 38, 662-674. https://doi.org/10.1016/j.molcel.2010.03.021
  57. Yu, T., Tang, B., and Sun, X. (2017). Development of inhibitors targeting hypoxia-inducible factor 1 and 2 for cancer therapy. Yonsei Med. J. 58, 489-496. https://doi.org/10.3349/ymj.2017.58.3.489
  58. Yu, W., Gius, D., Onyango, P., Muldoon-Jacobs, K., Karp, J., Feinberg, A.P., and Cui, H. (2008). Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451, 202-206. https://doi.org/10.1038/nature06468
  59. Yuan, S., Liu, Q., Hu, Z., Zhou, Z., Wang, G., Li, C., Xie, W., Meng, G., Xiang, Y., Wu, N., et al. (2018). Long non-coding RNA MUC5B-AS1 promotes metastasis through mutually regulating MUC5B expression in lung adenocarcinoma. Cell Death Dis. 9, 450. https://doi.org/10.1038/s41419-018-0472-6
  60. Zhang, P., Dong, Q., Zhu, H., Li, S., Shi, L., and Chen, X. (2019). Long noncoding antisense RNA GAS6-AS1 supports gastric cancer progression via increasing GAS6 expression. Gene 696, 1-9. https://doi.org/10.1016/j.gene.2018.12.079
  61. Zheng, Y., Wang, D.D., Wang, W., Pan, K., Huang, C.Y., Li, Y.F., Wang, Q.J., Yuan, S.Q., Jiang, S.S., Qiu, H.B., et al. (2014). Reduced expression of uroplakin 1A is associated with the poor prognosis of gastric adenocarcinoma patients. PLoS One 9, e93073. https://doi.org/10.1371/journal.pone.0093073
  62. Zhou, C., Ye, L., Jiang, C., Bai, J., Chi, Y., and Zhang, H. (2015). Long noncoding RNA HOTAIR, a hypoxia-inducible factor-1α activated driver of malignancy, enhances hypoxic cancer cell proliferation, migration, and invasion in non-small cell lung cancer. Tumour Biol. 36, 9179-9188. https://doi.org/10.1007/s13277-015-3453-8
  63. Zhu, G., Wang, S., Chen, J., Wang, Z., Liang, X., Wang, X., Jiang, J., Lang, J., and Li, L. (2017). Long noncoding RNA HAS2-AS1 mediates hypoxiainduced invasiveness of oral squamous cell carcinoma. Mol. Carcinog. 56, 2210-2222. https://doi.org/10.1002/mc.22674
  64. Zhu, H., Tang, Y., Zhang, X., Jiang, X., Wang, Y., Gan, Y., and Yang, J. (2015). Downregulation of UPK1A suppresses proliferation and enhances apoptosis of bladder transitional cell carcinoma cells. Med. Oncol. 32, 84. https://doi.org/10.1007/s12032-015-0541-y

피인용 문헌

  1. Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells vol.44, pp.10, 2020, https://doi.org/10.14348/molcells.2021.0093
  2. The regulatory role of antisense lncRNAs in cancer vol.21, pp.1, 2020, https://doi.org/10.1186/s12935-021-02168-4