DOI QR코드

DOI QR Code

BC200 RNA: An Emerging Therapeutic Target and Diagnostic Marker for Human Cancer

  • Shin, Heegwon ;
  • Kim, Youngmi ;
  • Kim, Meehyein ;
  • Lee, Younghoon
  • Received : 2018.11.27
  • Accepted : 2018.11.14
  • Published : 2018.12.31

Abstract

One of the most interesting findings from genome-wide expression analysis is that a considerable amount of noncoding RNA (ncRNA) is present in the cell. Recent studies have identified diverse biological functions of ncRNAs, which are expressed in a much wider array of forms than proteins. Certain ncRNAs associated with diseases, in particular, have attracted research attention as novel therapeutic targets and diagnostic markers. BC200 RNA, a 200-nucleotide ncRNA originally identified as a neuron-specific transcript, is abnormally over-expressed in several types of cancer tissue. A number of recent studies have suggested mechanisms by which abnormal expression of BC200 RNA contributes to the development of cancer. In this article, we first provide a brief review of a recent progress in identifying functions of BC200 RNA in cancer cells, and then offer examples of other ncRNAs as new therapeutic targets and diagnostic markers for human cancer. Finally, we discuss future directions of studies on BC200 RNA for new cancer treatments.

Keywords

BC200 RNA;cancer;diagnostic marker;ncRNA(noncoding RNA);therapeutic target

E1BJB7_2018_v41n12_993_f0001.png 이미지

Fig. 1. Schematic diagram of BC200 RNA.

E1BJB7_2018_v41n12_993_f0002.png 이미지

Fig. 2. Involvement of BC200 RNA in the genesis and development of cancers.

Table 1. Summary of clinical studies of BC200 RNA in cancer

E1BJB7_2018_v41n12_993_t0001.png 이미지

References

  1. Amin, V., Harris, R.A., Onuchic, V., Jackson, A.R., Charnecki, T., Paithankar, S., Lakshmi Subramanian, S., Riehle, K., Coarfa, C., and Milosavljevic, A. (2015). Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs. Nat. Commun. 6, 6370. https://doi.org/10.1038/ncomms7370
  2. Baer, C., Claus, R., and Plass, C. (2013). Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 73, 473-477. https://doi.org/10.1158/0008-5472.CAN-12-3731
  3. Balas, M.M., and Johnson, A.M. (2018). Exploring the mechanisms behind long noncoding RNAs and cancer. Noncoding RNA Res. 3, 108-117. https://doi.org/10.1016/j.ncrna.2018.03.001
  4. Bandres, E., Agirre, X., Bitarte, N., Ramirez, N., Zarate, R., Roman-Gomez, J., Prosper, F., and Garcia-Foncillas, J. (2009). Epigenetic regulation of microRNA expression in colorectal cancer. Int. J. Cancer 125, 2737-2743. https://doi.org/10.1002/ijc.24638
  5. Barh, D., Malhotra, R., Ravi, B., and Sindhurani, P. (2010). MicroRNA let-7: an emerging next-generation cancer therapeutic. Curr. Oncol. 17, 70-80.
  6. Beg, M.S., Brenner, A.J., Sachdev, J., Borad, M., Kang, Y.K., Stoudemire, J., Smith, S., Bader, A.G., Kim, S., and Hong, D.S. (2017). Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest. New Drugs 35, 180-188. https://doi.org/10.1007/s10637-016-0407-y
  7. Benjamin, H., Lebanony, D., Rosenwald, S., Cohen, L., Gibori, H., Barabash, N., Ashkenazi, K., Goren, E., Meiri, E., Morgenstern, S., et al. (2010). A diagnostic assay based on microRNA expression accurately identifies malignant pleural mesothelioma. J. Mol. Diagn. 12, 771-779. https://doi.org/10.2353/jmoldx.2010.090169
  8. Booy, E.P., McRae, E.K., Koul, A., Lin, F., and McKenna, S.A. (2017). The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol. Cancer 16, 109. https://doi.org/10.1186/s12943-017-0679-7
  9. Brase, J.C., Johannes, M., Schlomm, T., Falth, M., Haese, A., Steuber, T., Beissbarth, T., Kuner, R., and Sultmann, H. (2011). Circulating miRNAs are correlated with tumor progression in prostate cancer. Int. J. Cancer 128, 608-616. https://doi.org/10.1002/ijc.25376
  10. Briggs, J.A., Wolvetang, E.J., Mattick, J.S., Rinn, J.L., and Barry, G. (2015). Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron 88, 861-877. https://doi.org/10.1016/j.neuron.2015.09.045
  11. Brosnan, C.A., and Voinnet, O. (2009). The long and the short of noncoding RNAs. Curr. Opin. Cell Biol. 21, 416-425. https://doi.org/10.1016/j.ceb.2009.04.001
  12. Bushati, N., and Cohen, S.M. (2007). microRNA functions. Annu. Rev. Cell Dev. Biol. 23, 175-205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
  13. Chen, W., Bocker, W., Brosius, J., and Tiedge, H. (1997). Expression of neural BC200 RNA in human tumours. J. Pathol. 183, 345-351. https://doi.org/10.1002/(SICI)1096-9896(199711)183:3<345::AID-PATH930>3.0.CO;2-8
  14. Chen, X., Ba, Y., Ma, L., Cai, X., Yin, Y., Wang, K., Guo, J., Zhang, Y., Chen, J., Guo, X., et al. (2008). Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18, 997-1006. https://doi.org/10.1038/cr.2008.282
  15. Chen, X., Mangala, L.S., Rodriguez-Aguayo, C., Kong, X., Lopez-Berestein, G., and Sood, A.K. (2018). RNA interference-based therapy and its delivery systems. Cancer Metastasis Rev. 37, 107-124. https://doi.org/10.1007/s10555-017-9717-6
  16. Chung, S., Nakagawa, H., Uemura, M., Piao, L., Ashikawa, K., Hosono, N., Takata, R., Akamatsu, S., Kawaguchi, T., Morizono, T., et al. (2011). Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci. 102, 245-252. https://doi.org/10.1111/j.1349-7006.2010.01737.x
  17. Consortium, E.P. (2004). The ENCODE (ENCyclopedia Of DNA Elements) Project. Sci. 306, 636-640. https://doi.org/10.1126/science.1105136
  18. Derrien, T., Johnson, R., Bussotti, G., Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D.G., et al. (2012). The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775-1789. https://doi.org/10.1101/gr.132159.111
  19. Duning, K., Buck, F., Barnekow, A., and Kremerskothen, J. (2008). SYNCRIP, a component of dendritically localized mRNPs, binds to the translation regulator BC200 RNA. J. Neurochem. 105, 351-359. https://doi.org/10.1111/j.1471-4159.2007.05138.x
  20. Ebisuya, M., Yamamoto, T., Nakajima, M., and Nishida, E. (2008). Ripples from neighbouring transcription. Nat. Cell Biol. 10, 1106-1113. https://doi.org/10.1038/ncb1771
  21. Eom, T., Berardi, V., Zhong, J., Risuleo, G., and Tiedge, H. (2011). Dual nature of translational control by regulatory BC RNAs. Mol. Cell. Biol. 31, 4538-4549. https://doi.org/10.1128/MCB.05885-11
  22. Gu, L., Lu, L., Zhou, D., and Liu, Z. (2018). Long noncoding RNA BCYRN1 promotes the proliferation of colorectal cancer cells via upregulating NPR3 expression. Cell. Physiol. Biochem. 48, 2337-2349. https://doi.org/10.1159/000492649
  23. Gupta, R.A., Shah, N., Wang, K.C., Kim, J., Horlings, H.M., Wong, D.J., Tsai, M.C., Hung, T., Argani, P., Rinn, J.L., et al. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464, 1071-1076. https://doi.org/10.1038/nature08975
  24. Hajjari, M., and Salavaty, A. (2015). HOTAIR: an oncogenic long noncoding RNA in different cancers. Cancer Biol. Med. 12, 1-9.
  25. Hasanzadeh, M., Movahedi, M., Rejali, M., Maleki, F., Moetamani-Ahmadi, M., Seifi, S., Hosseini, Z., Khazaei, M., Amerizadeh, F., Ferns, G.A., et al. (2019). The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer. J. Cell Physiol. 234, 1289-1294. https://doi.org/10.1002/jcp.27160
  26. Hu, T., and Lu, Y.R. (2015). BCYRN1, a c-MYC-activated long noncoding RNA, regulates cell metastasis of non-small-cell lung cancer. Cancer Cell Int. 15, 36. https://doi.org/10.1186/s12935-015-0183-3
  27. Iacoangeli, A., Adzovic, L., Chen, E.Q., Latif Cattie, R., Soff, G.A., and Tiedge, H. (2018). Regulatory BC200 RNA in peripheral blood of patients with invasive breast cancer. J. Investig. Med. 66, 1055-1063. https://doi.org/10.1136/jim-2018-000717
  28. Iacoangeli, A., Lin, Y., Morley, E.J., Muslimov, I.A., Bianchi, R., Reilly, J., Weedon, J., Diallo, R., Bocker, W., and Tiedge, H. (2004). BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis 25, 2125-2133. https://doi.org/10.1093/carcin/bgh228
  29. Iorio, M.V., and Croce, C.M. (2012). MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol. Med. 4, 143-159. https://doi.org/10.1002/emmm.201100209
  30. Jain, S., Thakkar, N., Chhatai, J., Pal Bhadra, M., and Bhadra, U. (2017). Long non-coding RNA: Functional agent for disease traits. RNA Biol. 14, 522-535. https://doi.org/10.1080/15476286.2016.1172756
  31. Jang, S., Shin, H., Lee, J., Kim, Y., Bak, G., and Lee, Y. (2017). Regulation of BC200 RNA-mediated translation inhibition by hnRNP E1 and E2. FEBS Lett. 591, 393-405. https://doi.org/10.1002/1873-3468.12544
  32. Johnson, S.M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K.L., Brown, D., and Slack, F.J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120, 635-647. https://doi.org/10.1016/j.cell.2005.01.014
  33. Johnsson, P., and Morris, K.V. (2014). Expanding the functional role of long noncoding RNAs. Cell Res. 24, 1284-1285. https://doi.org/10.1038/cr.2014.104
  34. Kim, Y., Lee, J., Shin, H., Jang, S., Kim, S.C., and Lee, Y. (2017). Biosynthesis of brain cytoplasmic 200 RNA. Sci. Rep. 7, 6884. https://doi.org/10.1038/s41598-017-05097-3
  35. Ko, J.Y., Oh, S., and Yoo, K.H. (2017). Functional enhancers as master regulators of tissue-specific gene regulation and cancer Development. Mol. Cells 40, 169-177.
  36. Kogo, R., Shimamura, T., Mimori, K., Kawahara, K., Imoto, S., Sudo, T., Tanaka, F., Shibata, K., Suzuki, A., Komune, S., et al. (2011). Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 71, 6320-6326. https://doi.org/10.1158/0008-5472.CAN-11-1021
  37. Kondrashov, A.V., Kiefmann, M., Ebnet, K., Khanam, T., Muddashetty, R.S., and Brosius, J. (2005). Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP). J. Mol. Biol. 353, 88-103. https://doi.org/10.1016/j.jmb.2005.07.049
  38. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M.C., Baldwin, J., Devon, K., Dewar, K., Doyle, M., FitzHugh, W., et al. (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921. https://doi.org/10.1038/35057062
  39. Lee, Y.S., and Dutta, A. (2007). The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 21, 1025-1030. https://doi.org/10.1101/gad.1540407
  40. Li, P., Yang, B., Xia, S., Chen, L.-h., Ning, N., Ma, B., Liu, Q., Yang, H., Zhang, D.S.-z., and Du, X.N. (2016). BC200 RNA is over-expressed in colorectal cancer and promotes migration and invasion of HCT116 cells. Int. J. Clin. Exp. Patho. 9, 1481-1486.
  41. Lin, D., Pestova, T.V., Hellen, C.U., and Tiedge, H. (2008). Translational control by a small RNA: dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism. Mol. Cell. Biol. 28, 3008-3019. https://doi.org/10.1128/MCB.01800-07
  42. Long, L., Huang, G., Zhu, H., Guo, Y., Liu, Y., and Huo, J. (2013). Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2. J. Transl. Med. 11, 275. https://doi.org/10.1186/1479-5876-11-275
  43. Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B.L., Mak, R.H., Ferrando, A.A., et al. (2005). MicroRNA expression profiles classify human cancers. Nature 435, 834-838. https://doi.org/10.1038/nature03702
  44. Luo, P., Liu, X.F., Wang, Y.C., Li, N.D., Liao, S.J., Yu, M.X., Liang, C.Z., and Tu, J.C. (2017). Prognostic value of abnormally expressed lncRNAs in ovarian carcinoma: a systematic review and meta-analysis. Oncotarget 8, 23927-23936.
  45. Ma, J., Zhang, J., Weng, Y.C., and Wang, J.C. (2018). EZH2-Mediated microRNA-139-5p regulates epithelial-mesenchymal transition and lymph node metastasis of pancreatic cancer. Mol. Cells 41, 868-880.
  46. Mitomo, S., Maesawa, C., Ogasawara, S., Iwaya, T., Shibazaki, M., Yashima-Abo, A., Kotani, K., Oikawa, H., Sakurai, E., Izutsu, N., et al. (2008). Downregulation of miR-138 is associated with overexpression of human telomerase reverse transcriptase protein in human anaplastic thyroid carcinoma cell lines. Cancer Sci. 99, 280-286. https://doi.org/10.1111/j.1349-7006.2007.00666.x
  47. Muddashetty, R., Khanam, T., Kondrashov, A., Bundman, M., Iacoangeli, A., Kremerskothen, J., Duning, K., Barnekow, A., Huttenhofer, A., Tiedge, H., et al. (2002). Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. J. Mol. Biol. 321, 433-445. https://doi.org/10.1016/S0022-2836(02)00655-1
  48. Pasmant, E., Sabbagh, A., Vidaud, M., and Bieche, I. (2011). ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 25, 444-448. https://doi.org/10.1096/fj.10-172452
  49. Peng, J., Hou, F., Feng, J., Xu, S.X., and Meng, X.Y. (2018). Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo. Oncol. Lett. 15, 5809-5818.
  50. Qu, H., Xu, W., Huang, Y., and Yang, S. (2011). Circulating miRNAs: promising biomarkers of human cancer. Asian Pacific Journal of cancer prevention: APJCP 12, 1117-1125.
  51. Qureshi, I.A., and Mehler, M.F. (2012). Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nature reviews. Neuroscience 13, 528-541. https://doi.org/10.1038/nrn3234
  52. Ren, H., Yang, X., Yang, Y., Zhang, X., Zhao, R., Wei, R., Zhang, X., and Zhang, Y. (2018). Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma. Oncotarget 9, 4851-4861.
  53. Richter, J.D., and Klann, E. (2009). Making synaptic plasticity and memory last: mechanisms of translational regulation. Genes Dev. 23, 1-11. https://doi.org/10.1101/gad.1735809
  54. Samson, J., Cronin, S., and Dean, K. (2018). BC200 (BCYRN1) - The shortest, long, non-coding RNA associated with cancer. Noncoding RNA Res. 3, 131-143. https://doi.org/10.1016/j.ncrna.2018.05.003
  55. Schramm, L., and Hernandez, N. (2002). Recruitment of RNA polymerase III to its target promoters. Genes Dev. 16, 2593-2620. https://doi.org/10.1101/gad.1018902
  56. Shin, H., Lee, J., Kim, Y., Jang, S., Lee, Y., Kim, S., and Lee, Y. (2017). Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11. RNA Biol. 14, 1418-1430. https://doi.org/10.1080/15476286.2017.1297913
  57. Singh, R., Gupta, S.C., Peng, W.X., Zhou, N., Pochampally, R., Atfi, A., Watabe, K., Lu, Z., and Mo, Y.Y. (2016). Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis. Cell Death Dis. 7, e2262. https://doi.org/10.1038/cddis.2016.168
  58. Smalheiser, N.R. (2014). The RNA-centred view of the synapse: noncoding RNAs and synaptic plasticity. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 369.
  59. Song, W., and Zou, S.B. (2016). Prognostic role of lncRNA HOTAIR in esophageal squamous cell carcinoma. Clin. Chim. Acta. 463, 169-173. https://doi.org/10.1016/j.cca.2016.10.035
  60. Spector, Y., Fridman, E., Rosenwald, S., Zilber, S., Huang, Y., Barshack, I., Zion, O., Mitchell, H., Sanden, M., and Meiri, E. (2013). Development and validation of a microRNA-based diagnostic assay for classification of renal cell carcinomas. Mol. Oncol. 7, 732-738. https://doi.org/10.1016/j.molonc.2013.03.002
  61. Struhl, K. (2007). Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat. Struct. Mol. Biol. 14, 103-105. https://doi.org/10.1038/nsmb0207-103
  62. Sutcliffe, J.G., Milner, R.J., Bloom, F.E., and Lerner, R.A. (1982). Common 82-nucleotide sequence unique to brain RNA. Proc. Natl. Acad. Sci. USA 79, 4942-4946. https://doi.org/10.1073/pnas.79.16.4942
  63. Sutcliffe, J.G., Milner, R.J., Gottesfeld, J.M., and Lerner, R.A. (1984). Identifier sequences are transcribed specifically in brain. Nature 308, 237-241. https://doi.org/10.1038/308237a0
  64. Tiedge, H., Chen, W., and Brosius, J. (1993). Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. J. Neurosci. 13, 2382-2390. https://doi.org/10.1523/JNEUROSCI.13-06-02382.1993
  65. Volinia, S., Calin, G.A., Liu, C.G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA 103, 2257-2261. https://doi.org/10.1073/pnas.0510565103
  66. Wapinski, O., and Chang, H.Y. (2011). Long noncoding RNAs and human disease. Trends Cell Biol. 21, 354-361. https://doi.org/10.1016/j.tcb.2011.04.001
  67. Ward, L.D., and Kellis, M. (2012). Interpreting noncoding genetic variation in complex traits and human disease. Nat. Biotechnol. 30, 1095-1106. https://doi.org/10.1038/nbt.2422
  68. Watson, J.B., and Sutcliffe, J.G. (1987). Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol. Cell. Biol. 7, 3324-3327. https://doi.org/10.1128/MCB.7.9.3324
  69. Wilusz, J.E., Sunwoo, H., and Spector, D.L. (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494-1504. https://doi.org/10.1101/gad.1800909
  70. Wu, D.I., Wang, T., Ren, C., Liu, L., Kong, D., Jin, X., Li, X., and Zhang, G. (2016). Downregulation of BC200 in ovarian cancer contributes to cancer cell proliferation and chemoresistance to carboplatin. Oncol. Lett. 11, 1189-1194. https://doi.org/10.3892/ol.2015.3983
  71. Wu, K., Xu, K., Liu, K., Huang, J., Chen, J., Zhang, J., and Zhang, N. (2018). Long noncoding RNA BC200 regulates cell growth and invasion in colon cancer. Int. J. Biochem. Cell Biol. 99, 219-225. https://doi.org/10.1016/j.biocel.2018.04.001
  72. Wu, Z., Liu, X., Liu, L., Deng, H., Zhang, J., Xu, Q., Cen, B., and Ji, A. (2014). Regulation of lncRNA expression. Cell Mol. Biol. Lett. 19, 561-575.
  73. Zhang, H., Zhang, H., Zhao, M., Lv, Z., Zhang, X., Qin, X., Wang, H., Wang, S., Su, J., Lv, X., et al. (2013). MiR-138 inhibits tumor growth through repression of EZH2 in non-small cell lung cancer. Cell Physiol. Biochem. 31, 56-65. https://doi.org/10.1159/000343349
  74. Zhang, Y., Wang, L.J., Li, W.F., Zhang, X., and Yang, X.J. (2018). The prognostic value of HOTAIR for predicting long-term prognosis of patients with gastrointestinal cancers. Medicine (Baltimore) 97, e11139. https://doi.org/10.1097/MD.0000000000011139
  75. Zhao, R.H., Zhu, C.H., Li, X.K., Cao, W., Zong, H., Cao, X.G., and Hu, H.Y. (2016). BC200 LncRNA a potential predictive marker of poor prognosis in esophageal squamous cell carcinoma patients. Onco. Targets Ther. 9, 2221-2226.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF), MSIT