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Open Access 01-03-2014 | NON-THEMATIC REVIEW

The non-coding transcriptome as a dynamic regulator of cancer metastasis

Authors: Francesco Crea, Pier Luc Clermont, Abhijit Parolia, Yuzhuo Wang, Cheryl D. Helgason

Published in: Cancer and Metastasis Reviews | Issue 1/2014

Abstract

Since the discovery of microRNAs, non-coding RNAs (NC-RNAs) have increasingly attracted the attention of cancer investigators. Two classes of NC-RNAs are emerging as putative metastasis-related genes: long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). LncRNAs orchestrate metastatic progression through several mechanisms, including the interaction with epigenetic effectors, splicing control and generation of microRNA-like molecules. In contrast, snoRNAs have been long considered “housekeeping” genes with no relevant function in cancer. However, recent evidence challenges this assumption, indicating that some snoRNAs are deregulated in cancer cells and may play a specific role in metastasis. Interestingly, snoRNAs and lncRNAs share several mechanisms of action, and might synergize with protein-coding genes to generate a specific cellular phenotype. This evidence suggests that the current paradigm of metastatic progression is incomplete. We propose that NC-RNAs are organized in complex interactive networks which orchestrate cellular phenotypic plasticity. Since plasticity is critical for cancer cell metastasis, we suggest that a molecular interactome composed by both NC-RNAs and proteins orchestrates cancer metastasis. Interestingly, expression of lncRNAs and snoRNAs can be detected in biological fluids, making them potentially useful biomarkers. NC-RNA expression profiles in human neoplasms have been associated with patients’ prognosis. SnoRNA and lncRNA silencing in pre-clinical models leads to cancer cell death and/or metastasis prevention, suggesting they can be investigated as novel therapeutic targets. Based on the literature to date, we critically discuss how the NC-RNA interactome can be explored and manipulated to generate more effective diagnostic, prognostic, and therapeutic strategies for metastatic neoplasms.

Crick, F. (1970). Central dogma of molecular biology. Nature, 227, 561–563.PubMed

Ponting, C. P., & Belgard, T. G. (2010). Transcribed dark matter: meaning or myth? Human Molecular Genetics, 19, R162–R168.PubMedCentralPubMed

Birney, E., Stamatoyannopoulos, J. A., Dutta, A., Guigo, R., Gingeras, T. R., Margulies, E. H., et al. (2007). Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 447, 799–816.PubMed

Brase, J. C., Johannes, M., Schlomm, T., Falth, M., Haese, A., Steuber, T., et al. (2011). Circulating miRNAs are correlated with tumor progression in prostate cancer. International Journal of Cancer, 128, 608–616.

Brase, J. C., Wuttig, D., Kuner, R., & Sultmann, H. (2010). Serum microRNAs as non-invasive biomarkers for cancer. Molecular Cancer, 9, 306.PubMedCentralPubMed

Catto, J. W., Alcaraz, A., Bjartell, A. S., De Vere, W. R., Evans, C. P., Fussel, S., et al. (2011). MicroRNA in prostate, bladder, and kidney cancer: a systematic review. European Urology, 59, 671–681.PubMed

Ma L, Bajic VB, Zhang Z (2013). On the classification of long non-coding RNAs RNA biology 10

Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., et al. (2005). The transcriptional landscape of the mammalian genome. Science, 309, 1559–1563.PubMed

Batista, P. J., & Chang, H. Y. (2013). Long noncoding RNAs: cellular address codes in development and disease. Cell, 152, 1298–1307.PubMedCentralPubMed

10.

Gibb, E. A., Brown, C. J., & Lam, W. L. (2011). The functional role of long non-coding RNA in human carcinomas. Molecular cancer, 10, 38.PubMedCentralPubMed

11.

Kiss, T. (2002). Small nucleolar RNAs: an abundant group of noncoding RNAs with diverse cellular functions. Cell, 109, 145–148.PubMed

12.

Williams, G. T., & Farzaneh, F. (2012). Are snoRNAs and snoRNA host genes new players in cancer? Nature reviews Cancer, 12, 84–88.PubMed

13.

Gee, H. E., Buffa, F. M., Camps, C., Ramachandran, A., Leek, R., Taylor, M., et al. (2011). The small-nucleolar RNAs commonly used for microRNA normalisation correlate with tumour pathology and prognosis. British journal of cancer, 104, 1168–1177.PubMedCentralPubMed

14.

Scott, M. S., & Ono, M. (2011). From snoRNA to miRNA: dual function regulatory non-coding RNAs. Biochimie, 93, 1987–1992.PubMedCentralPubMed

15.

Brameier, M., Herwig, A., Reinhardt, R., Walter, L., & Gruber, J. (2011). Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Research, 39, 675–686.PubMedCentralPubMed

16.

Ono, M., Scott, M. S., Yamada, K., Avolio, F., Barton, G. J., & Lamond, A. I. (2011). Identification of human miRNA precursors that resemble box C/D snoRNAs. Nucleic Acids Res, 39, 3879–3891.PubMedCentralPubMed

17.

Mannoor, K., Liao, J., & Jiang, F. (2012). Small nucleolar RNAs in cancer. Biochimica et biophysica acta, 1826, 121–128.PubMed

18.

Mehlen, P., & Puisieux, A. (2006). Metastasis: a question of life or death. Nature reviews Cancer, 6, 449–458.PubMed

19.

Chaffer, C. L., & Weinberg, R. A. (2011). A perspective on cancer cell metastasis. Science, 331, 1559–1564.PubMed

20.

Spano, D., Heck, C., De Antonellis, P., Christofori, G., & Zollo, M. (2012). Molecular networks that regulate cancer metastasis. Seminars in cancer biology, 22, 234–249.PubMed

21.

Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., et al. (2007). Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449, 557–563.PubMed

22.

Turajlic, S., Furney, S. J., Lambros, M. B., Mitsopoulos, C., Kozarewa, I., Geyer, F. C., et al. (2012). Whole genome sequencing of matched primary and metastatic acral melanomas. Genome research, 22, 196–207.PubMedCentralPubMed

23.

Nyormoi, O., & Bar-Eli, M. (2003). Transcriptional regulation of metastasis-related genes in human melanoma. Clinical & experimental metastasis, 20, 251–263.

24.

Bernards, R., & Weinberg, R. A. (2002). A progression puzzle. Nature, 418, 823.PubMed

25.

Silvera, D., Formenti, S. C., & Schneider, R. J. (2010). Translational control in cancer. Nature reviews Cancer, 10, 254–266.PubMed

26.

Cao, P. D., Cheung, W. K., & Nguyen, D. X. (2011). Cell lineage specification in tumor progression and metastasis. Discovery medicine, 12, 329–340.PubMed

27.

Lujambio, A., & Esteller, M. (2009). How epigenetics can explain human metastasis: a new role for microRNAs. Cell Cycle, 8, 377–382.PubMed

28.

Tahira, A. C., Kubrusly, M. S., Faria, M. F., Dazzani, B., Fonseca, R. S., Maracaja-Coutinho, V., et al. (2011). Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer. Molecular cancer, 10, 141.PubMedCentralPubMed

29.

Matouk, I. J., Abbasi, I., Hochberg, A., Galun, E., Dweik, H., & Akkawi, M. (2009). Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis. European journal of gastroenterology & hepatology, 21, 688–692.

30.

Bhartiya D, Pal K, Ghosh S, Kapoor S, Jalali S, Panwar B, Jain S, Sati S, Sengupta S, Sachidanandan C, et al. (2013). lncRNome: a comprehensive knowledgebase of human long noncoding RNAs Database : the journal of biological databases and curation 2013, bat034.

31.

Chen, G., Wang, Z., Wang, D., Qiu, C., Liu, M., Chen, X., et al. (2013). LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Research, 41, D983–D986.PubMedCentralPubMed

32.

Gittelman M, Hertzman B, Bailen J, Williams T, Koziol I, Henderson RJ, Efros M, Bidair M, Ward JF (2013). PROGENSA(R)PCA3 molecular urine test as a predictor of repeat prostate biopsy outcome in men with previous negative biopsies: a prospective multicenter clinical study. The Journal of urology.

33.

Du, Z., Fei, T., Verhaak, R. G., Su, Z., Zhang, Y., Brown, M., et al. (2013). Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer. Nature Structural & Molecular Biology, 20, 908–913.

34.

Tsai, M. C., Spitale, R. C., & Chang, H. Y. (2011). Long intergenic noncoding RNAs: new links in cancer progression. Cancer research, 71, 3–7.PubMedCentralPubMed

35.

Ji, P., Diederichs, S., Wang, W., Boing, S., Metzger, R., Schneider, P. M., et al. (2003). MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22, 8031–8041.PubMed

36.

Han, Y., Liu, Y., Nie, L., Gui, Y., & Cai, Z. (2013). Inducing cell proliferation inhibition, apoptosis, and motility reduction by silencing long noncoding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 in urothelial carcinoma of the bladder. Urology, 81(209), e201–e207.

37.

Feng, J., Tian, L., Sun, Y., Li, D., Wu, T., Wang, Y., et al. (2012). Expression of long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript-1 is correlated with progress and apoptosis of laryngeal squamous cell carcinoma. Head & neck oncology, 4, 46.

38.

Schmidt, L. H., Spieker, T., Koschmieder, S., Schaffers, S., Humberg, J., Jungen, D., et al. (2011). The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer, 6, 1984–1992.

39.

Gupta, R. A., Shah, N., Wang, K. C., Kim, J., Horlings, H. M., Wong, D. J., et al. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 464, 1071–1076.PubMedCentralPubMed

40.

Xu, Z. Y., Yu, Q. M., Du, Y. A., Yang, L. T., Dong, R. Z., Huang, L., et al. (2013). Knockdown of long non-coding RNA HOTAIR suppresses tumor invasion and reverses epithelial-mesenchymal transition in gastric cancer. International Journal of Biological Sciences, 9, 587–597.PubMedCentralPubMed

41.

Nakagawa, T., Endo, H., Yokoyama, M., Abe, J., Tamai, K., Tanaka, N., et al. (2013). Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochemical and biophysical research communications, 436, 319–324.PubMed

42.

Yang, Z., Zhou, L., Wu, L. M., Lai, M. C., Xie, H. Y., Zhang, F., et al. (2011). Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Annals of surgical oncology, 18, 1243–1250.PubMed

43.

Park, S. M., Park, S. J., Kim, H. J., Kwon, O. H., Kang, T. W., Sohn, H. A., et al. (2013). A known expressed sequence tag, BM742401, is a potent lincRNA inhibiting cancer metastasis. Experimental & Molecular Medicine, 45, e31.

44.

Cheetham, S. W., Gruhl, F., Mattick, J. S., & Dinger, M. E. (2013). Long noncoding RNAs and the genetics of cancer. British journal of cancer, 108, 2419–2425.PubMedCentralPubMed

45.

Chung, S., Nakagawa, H., Uemura, M., Piao, L., Ashikawa, K., Hosono, N., et al. (2011). Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer science, 102, 245–252.PubMed

46.

Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis R, Nishida N, Gafa R, Song J, Guo Z, et al. (2013). CCAT2, a novel non-coding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer Genome research.

47.

Bertucci, F., Lagarde, A., Ferrari, A., Finetti, P., Charafe-Jauffret, E., Van Laere, S., et al. (2012). 8q24 cancer risk allele associated with major metastatic risk in inflammatory breast cancer. PloS one, 7, e37943.PubMedCentralPubMed

48.

Qiu, M. T., Hu, J. W., Yin, R., & Xu, L. (2013). Long noncoding RNA: an emerging paradigm of cancer research. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine, 34, 613–620.

49.

Ponting, C. P., Oliver, P. L., & Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell, 136, 629–641.PubMed

50.

Tsai, M. C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., et al. (2010). Long noncoding RNA as modular scaffold of histone modification complexes. Science, 329, 689–693.PubMedCentralPubMed

51.

Luo, M., Li, Z., Wang, W., Zeng, Y., Liu, Z., & Qiu, J. (2013). Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer letters, 333, 213–221.PubMed

52.

Chisholm, K. M., Wan, Y., Li, R., Montgomery, K. D., Chang, H. Y., & West, R. B. (2012). Detection of long non-coding RNA in archival tissue: correlation with polycomb protein expression in primary and metastatic breast carcinoma. PloS one, 7, e47998.PubMedCentralPubMed

53.

Benetatos, L., Voulgaris, E., Vartholomatos, G., & Hatzimichael, E. (2013). Non-coding RNAs and EZH2 interactions in cancer: long and short tales from the transcriptome. International journal of cancer Journal international du cancer, 133, 267–274.PubMed

54.

Brockdorff, N. (2013). Noncoding RNA and polycomb recruitment. RNA, 19, 429–442.PubMedCentralPubMed

55.

Crea, F., Hurt, E. M., Mathews, L. A., Cabarcas, S. M., Sun, L., Marquez, V. E., et al. (2011). Pharmacologic disruption of polycomb repressive complex 2 inhibits tumorigenicity and tumor progression in prostate cancer. Molecular cancer, 10, 40.PubMedCentralPubMed

56.

Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., et al. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences of the United States of America, 106, 11667–11672.PubMedCentralPubMed

57.

Yap, K. L., Li, S., Munoz-Cabello, A. M., Raguz, S., Zeng, L., Mujtaba, S., et al. (2010). Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Molecular cell, 38, 662–674.PubMedCentralPubMed

58.

Yang, L., Lin, C., Liu, W., Zhang, J., Ohgi, K. A., Grinstein, J. D., et al. (2011). ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell, 147, 773–788.PubMedCentralPubMed

59.

Aguilo, F., Zhou, M. M., & Walsh, M. J. (2011). Long noncoding RNA, polycomb, and the ghosts haunting INK4b-ARF-INK4a expression. Cancer research, 71, 5365–5369.PubMedCentralPubMed

60.

Royo, H., & Cavaille, J. (2008). Non-coding RNAs in imprinted gene clusters. Biology of the cell/under the auspices of the European Cell Biology Organization, 100, 149–166.PubMed

61.

Brannan, C. I., Dees, E. C., Ingram, R. S., & Tilghman, S. M. (1990). The product of the H19 gene may function as an RNA. Molecular and cellular biology, 10, 28–36.PubMedCentralPubMed

62.

Sasaki, H., Ishihara, K., & Kato, R. (2000). Mechanisms of Igf2/H19 imprinting: DNA methylation, chromatin and long-distance gene regulation. Journal of biochemistry, 127, 711–715.PubMed

63.

Cui, H., Onyango, P., Brandenburg, S., Wu, Y., Hsieh, C. L., & Feinberg, A. P. (2002). Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer research, 62, 6442–6446.PubMed

64.

Lu, Y., Lu, P., Zhu, Z., Xu, H., & Zhu, X. (2009). Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer. Journal of experimental & clinical cancer research : CR, 28, 125.PubMedCentral

65.

Moulton, T., Crenshaw, T., Hao, Y., Moosikasuwan, J., Lin, N., Dembitzer, F., et al. (1994). Epigenetic lesions at the H19 locus in Wilms’ tumour patients. Nature genetics, 7, 440–447.PubMed

66.

Fellig, Y., Ariel, I., Ohana, P., Schachter, P., Sinelnikov, I., Birman, T., et al. (2005). H19 expression in hepatic metastases from a range of human carcinomas. Journal of clinical pathology, 58, 1064–1068.PubMedCentralPubMed

67.

Matouk, I. J., Mezan, S., Mizrahi, A., Ohana, P., Abu-Lail, R., Fellig, Y., et al. (2010). The oncofetal H19 RNA connection: hypoxia, p53 and cancer. Biochimica et biophysica acta, 1803, 443–451.PubMed

68.

Barsyte-Lovejoy, D., Lau, S. K., Boutros, P. C., Khosravi, F., Jurisica, I., Andrulis, I. L., et al. (2006). The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer research, 66, 5330–5337.PubMed

69.

Berteaux, N., Lottin, S., Monte, D., Pinte, S., Quatannens, B., Coll, J., et al. (2005). H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. The Journal of biological chemistry, 280, 29625–29636.PubMed

70.

Amit, D., & Hochberg, A. (2010). Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences. Journal of translational medicine, 8, 134.PubMedCentralPubMed

71.

Mizrahi, A., Czerniak, A., Levy, T., Amiur, S., Gallula, J., Matouk, I., et al. (2009). Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. Journal of Translational Medicine, 7, 69.PubMedCentralPubMed

72.

Scaiewicz V, Sorin V, Fellig Y, Birman T, Mizrahi A, Galula J, Abu-Lail R, Shneider T, Ohana P, Buscail L, et al. (2010). Use of H19 gene regulatory sequences in DNA-based therapy for pancreatic cancer Journal of oncology 2010, 178174.

73.

Sorin, V., Ohana, P., Mizrahi, A., Matouk, I., Birman, T., Hochberg, A., et al. (2011). Regional therapy with DTA-H19 vector suppresses growth of colon adenocarcinoma metastases in the rat liver. International journal of oncology, 39, 1407–1412.PubMed

74.

Matouk, I., Raveh, E., Ohana, P., Lail, R. A., Gershtain, E., Gilon, M., et al. (2013). The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. International Journal of Molecular Sciences, 14, 4298–4316.PubMedCentralPubMed

75.

Matouk, I., Ayesh, B., Schneider, T., Ayesh, S., Ohana, P., de-Groot, N., et al. (2004). Oncofetal splice-pattern of the human H19 gene. Biochemical and Biophysical Research Communications, 318, 916–919.PubMed

76.

Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013). Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression Cancer letters.

77.

Cai, X., & Cullen, B. R. (2007). The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA, 13, 313–316.PubMedCentralPubMed

78.

Tsang, W. P., Ng, E. K., Ng, S. S., Jin, H., Yu, J., Sung, J. J., et al. (2010). Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis, 31, 350–358.PubMed

79.

Li, D., Feng, J., Wu, T., Wang, Y., Sun, Y., Ren, J., et al. (2013). Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. The American Journal of Pathology, 182, 64–70.PubMed

80.

Guil, S., & Esteller, M. (2012). Cis-acting noncoding RNAs: friends and foes. Nature structural & molecular biology, 19, 1068–1075.

81.

Congrains, A., Kamide, K., Ohishi, M., & Rakugi, H. (2013). ANRIL: molecular mechanisms and implications in human health. International Journal of Molecular Sciences, 14, 1278–1292.PubMedCentralPubMed

82.

Kotake, Y., Nakagawa, T., Kitagawa, K., Suzuki, S., Liu, N., Kitagawa, M., et al. (2011). Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene, 30, 1956–1962.PubMedCentralPubMed

83.

Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., et al. (2007). The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. Genes & development, 21, 525–530.

84.

O’Loghlen, A., Munoz-Cabello, A. M., Gaspar-Maia, A., Wu, H. A., Banito, A., Kunowska, N., et al. (2012). MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation. Cell stem cell, 10, 33–46.PubMedCentralPubMed

85.

Gil, J., Bernard, D., Martinez, D., & Beach, D. (2004). Polycomb CBX7 has a unifying role in cellular lifespan. Nature cell biology, 6, 67–72.PubMed

86.

Darini, C. Y., Pisani, D. F., Hofman, P., Pedeutour, F., Sudaka, I., Chomienne, C., et al. (2012). Self-renewal gene tracking to identify tumour-initiating cells associated with metastatic potential. Oncogene, 31, 2438–2449.PubMed

87.

Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell, 133, 704–715.PubMedCentralPubMed

88.

Anko, M. L., & Neugebauer, K. M. (2010). Long noncoding RNAs add another layer to pre-mRNA splicing regulation. Molecular cell, 39, 833–834.PubMed

89.

Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., et al. (2008). A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial–mesenchymal transition. Genes & development, 22, 756–769.

90.

Huarte, M., & Rinn, J. L. (2010). Large non-coding RNAs: missing links in cancer? Human molecular genetics, 19, R152–R161.PubMedCentralPubMed

91.

Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., et al. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecular cell, 7, 1267–1278.PubMed

92.

Vandewalle, C., Comijn, J., De Craene, B., Vermassen, P., Bruyneel, E., Andersen, H., et al. (2005). SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell–cell junctions. Nucleic acids research, 33, 6566–6578.PubMedCentralPubMed

93.

Hutchinson, J. N., Ensminger, A. W., Clemson, C. M., Lynch, C. R., Lawrence, J. B., & Chess, A. (2007). A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC genomics, 8, 39.PubMedCentralPubMed

94.

Tripathi, V., Ellis, J. D., Shen, Z., Song, D. Y., Pan, Q., Watt, A. T., et al. (2010). The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Molecular cell, 39, 925–938.PubMed

95.

Lin, R., Roychowdhury-Saha, M., Black, C., Watt, A. T., Marcusson, E. G., Freier, S. M., et al. (2011). Control of RNA processing by a large non-coding RNA over-expressed in carcinomas. FEBS letters, 585, 671–676.PubMedCentralPubMed

96.

Gutschner, T., Hammerle, M., Eissmann, M., Hsu, J., Kim, Y., Hung, G., et al. (2013). The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer research, 73, 1180–1189.PubMedCentralPubMed

97.

Tano, K., Mizuno, R., Okada, T., Rakwal, R., Shibato, J., Masuo, Y., et al. (2010). MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS letters, 584, 4575–4580.PubMed

98.

Ying, L., Chen, Q., Wang, Y., Zhou, Z., Huang, Y., & Qiu, F. (2012). Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Molecular Biosystems, 8, 2289–2294.PubMed

99.

Yang, M. H., Hsu, D. S., Wang, H. W., Wang, H. J., Lan, H. Y., Yang, W. H., et al. (2010). Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition. Nature Cell Biology, 12, 982–992.PubMed

100.

Wilusz, J. E., Freier, S. M., & Spector, D. L. (2008). 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell, 135, 919–932.PubMedCentralPubMed

101.

Mercer, T. R., & Mattick, J. S. (2013). Structure and function of long noncoding RNAs in epigenetic regulation. Nature Structural & Molecular Biology, 20, 300–307.

102.

Gutschner, T., & Diederichs, S. (2012). The hallmarks of cancer: a long non-coding RNA point of view. RNA Biology, 9, 703–719.PubMedCentralPubMed

103.

Petrov, D. A., & Hartl, D. L. (2000). Pseudogene evolution and natural selection for a compact genome. The Journal of Heredity, 91, 221–227.PubMed

104.

Ala, U., Karreth, F. A., Bosia, C., Pagnani, A., Taulli, R., Leopold, V., et al. (2013). Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proceedings of the National Academy of Sciences of the United States of America, 110, 7154–7159.PubMedCentralPubMed

105.

Salmena, L., Poliseno, L., Tay, Y., Kats, L., & Pandolfi, P. P. (2011). A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 146, 353–358.PubMedCentralPubMed

106.

Poliseno, L., Salmena, L., Zhang, J., Carver, B., Haveman, W. J., & Pandolfi, P. P. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature, 465, 1033–1038.PubMedCentralPubMed

107.

Karreth, F. A., Tay, Y., Perna, D., Ala, U., Tan, S. M., Rust, A. G., et al. (2011). In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell, 147, 382–395.

108.

Tay, Y., Kats, L., Salmena, L., Weiss, D., Tan, S. M., Ala, U., et al. (2011). Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell, 147, 344–357.PubMedCentralPubMed

109.

Kanamori, Y., Kigawa, J., Itamochi, H., Shimada, M., Takahashi, M., Kamazawa, S., et al. (2001). Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma. Clinical cancer research: an official journal of the American Association for Cancer Research, 7, 892–895.

110.

Tang, J. M., He, Q. Y., Guo, R. X., & Chang, X. J. (2006). Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer, 51, 181–191.PubMed

111.

Song, M. S., Salmena, L., & Pandolfi, P. P. (2012). The functions and regulation of the PTEN tumour suppressor. Nature reviews Molecular cell biology, 13, 283–296.PubMed

112.

Tan, X., Wang, S., Yang, B., Zhu, L., Yin, B., Chao, T., et al. (2012). The CREB-miR-9 negative feedback minicircuitry coordinates the migration and proliferation of glioma cells. PloS one, 7, e49570.PubMedCentralPubMed

113.

Laneve, P., Gioia, U., Andriotto, A., Moretti, F., Bozzoni, I., & Caffarelli, E. (2010). A minicircuitry involving REST and CREB controls miR-9-2 expression during human neuronal differentiation. Nucleic acids research, 38, 6895–6905.PubMedCentralPubMed

114.

Yang, F., Huo, X. S., Yuan, S. X., Zhang, L., Zhou, W. P., Wang, F., et al. (2013). Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Molecular cell, 49, 1083–1096.PubMed

115.

Kuwano, Y., Pullmann, R., Jr., Marasa, B. S., Abdelmohsen, K., Lee, E. K., Yang, X., et al. (2010). NF90 selectively represses the translation of target mRNAs bearing an AU-rich signature motif. Nucleic Acids Research, 38, 225–238.PubMedCentralPubMed

116.

Vumbaca, F., Phoenix, K. N., Rodriguez-Pinto, D., Han, D. K., & Claffey, K. P. (2008). Double-stranded RNA-binding protein regulates vascular endothelial growth factor mRNA stability, translation, and breast cancer angiogenesis. Molecular and Cellular Biology, 28, 772–783.PubMedCentralPubMed

117.

Huang, J. F., Guo, Y. J., Zhao, C. X., Yuan, S. X., Wang, Y., Tang, G. N., et al. (2013). Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin. Hepatology, 57, 1882–1892.PubMed

118.

Mendez, M. G., Kojima, S., & Goldman, R. D. (2010). Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 24, 1838–1851.

119.

Hall, A. (2009). The cytoskeleton and cancer. Cancer Metastasis Reviews, 28, 5–14.PubMed

120.

Yuan, S. X., Yang, F., Yang, Y., Tao, Q. F., Zhang, J., Huang, G., et al. (2012). Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology, 56, 2231–2241.PubMed

121.

Lay, A. J., Jiang, X. M., Kisker, O., Flynn, E., Underwood, A., Condron, R., et al. (2000). Phosphoglycerate kinase acts in tumour angiogenesis as a disulphide reductase. Nature, 408, 869–873.PubMed

122.

Crea, F., Fornaro, L., Bocci, G., Sun, L., Farrar, W. L., Falcone, A., et al. (2012). EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer metastasis reviews, 31, 753–761.PubMed

123.

Lafontaine, D. L., & Tollervey, D. (1998). Birth of the snoRNPs: the evolution of the modification-guide snoRNAs. Trends in biochemical sciences, 23, 383–388.PubMed

124.

Bachellerie, J. P., Cavaille, J., & Huttenhofer, A. (2002). The expanding snoRNA world. Biochimie, 84, 775–790.PubMed

125.

Ciganda, M., & Williams, N. (2011). Eukaryotic 5S rRNA biogenesis Wiley interdisciplinary reviews. RNA, 2, 523–533.PubMedCentralPubMed

126.

Makarova, J. A., & Kramerov, D. A. (2011). SNOntology: myriads of novel snoRNAs or just a mirage? BMC genomics, 12, 543.PubMedCentralPubMed

127.

Zhang, Y., Liu, J., Jia, C., Li, T., Wu, R., Wang, J., et al. (2010). Systematic identification and evolutionary features of rhesus monkey small nucleolar RNAs. BMC genomics, 11, 61.PubMedCentralPubMed

128.

Khanna, A., & Stamm, S. (2010). Regulation of alternative splicing by short non-coding nuclear RNAs. RNA Biology, 7, 480–485.PubMedCentralPubMed

129.

Kishore, S., Khanna, A., Zhang, Z., Hui, J., Balwierz, P. J., Stefan, M., et al. (2010). The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates alternative splicing. Human molecular genetics, 19, 1153–1164.PubMedCentralPubMed

130.

Cassidy, S. B., Schwartz, S., Miller, J. L., & Driscoll, D. J. (2012). Prader-Willi syndrome. Genetics in medicine: official journal of the American College of Medical Genetics, 14, 10–26.

131.

Nickerson ML, Im KM, Misner KJ, Tan W, Lou H, Gold B, Wells DW, Bravo HC, Fredrikson KM, Harkins TT, et al. (2013). Somatic alterations contributing to metastasis of a castration-resistant prostate cancer human mutation.

132.

Tavassoli, P., Wafa, L. A., Cheng, H., Zoubeidi, A., Fazli, L., Gleave, M., et al. (2010). TAF1 differentially enhances androgen receptor transcriptional activity via its N-terminal kinase and ubiquitin-activating and -conjugating domains. Molecular Endocrinology, 24, 696–708.PubMed

133.

Ender, C., Krek, A., Friedlander, M. R., Beitzinger, M., Weinmann, L., Chen, W., et al. (2008). A human snoRNA with microRNA-like functions. Molecular cell, 32, 519–528.PubMed

134.

Michel, C. I., Holley, C. L., Scruggs, B. S., Sidhu, R., Brookheart, R. T., Listenberger, L. L., et al. (2011). Small nucleolar RNAs U32a, U33, and U35a are critical mediators of metabolic stress. Cell metabolism, 14, 33–44.PubMedCentralPubMed

135.

Esteller, M. (2011). Non-coding RNAs in human disease. Nature reviews Genetics, 12, 861–874.PubMed

136.

Taulli, R., & Pandolfi, P. P. (2012). “Snorkeling” for missing players in cancer. The Journal of clinical investigation, 122, 2765–2768.PubMedCentralPubMed

137.

Chang, K. H., Mestdagh, P., Vandesompele, J., Kerin, M. J., & Miller, N. (2010). MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC cancer, 10, 173.PubMedCentralPubMed

138.

Ferreira, H. J., Heyn, H., Moutinho, C., & Esteller, M. (2012). CpG island hypermethylation-associated silencing of small nucleolar RNAs in human cancer. RNA biology, 9, 881–890.PubMedCentralPubMed

139.

Dong, X. Y., Rodriguez, C., Guo, P., Sun, X., Talbot, J. T., Zhou, W., et al. (2008). SnoRNA U50 is a candidate tumor-suppressor gene at 6q14.3 with a mutation associated with clinically significant prostate cancer. Human molecular genetics, 17, 1031–1042.PubMedCentralPubMed

140.

Dong, X. Y., Guo, P., Boyd, J., Sun, X., Li, Q., Zhou, W., et al. (2009). Implication of snoRNA U50 in human breast cancer. Journal of genetics and genomics = Yi chuan xue bao, 36, 447–454.PubMedCentralPubMed

141.

Mei, Y. P., Liao, J. P., Shen, J., Yu, L., Liu, B. L., Liu, L., et al. (2012). Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene, 31, 2794–2804.PubMed

142.

Chu, L., Su, M. Y., Maggi, L. B., Jr., Lu, L., Mullins, C., Crosby, S., et al. (2012). Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress. The Journal of clinical investigation, 122, 2793–2806.PubMedCentralPubMed

143.

Zong, X., Tripathi, V., & Prasanth, K. V. (2011). RNA splicing control: yet another gene regulatory role for long nuclear noncoding RNAs. RNA biology, 8, 968–977.PubMedCentralPubMed

144.

Lovat, F., Valeri, N., & Croce, C. M. (2011). MicroRNAs in the pathogenesis of cancer. Seminars in oncology, 38, 724–733.PubMed

145.

Davison, C. A., Durbin, S. M., Thau, M. R., Zellmer, V. R., Chapman, S. E., Diener, J., et al. (2013). Antioxidant enzymes mediate survival of breast cancer cells deprived of extracellular matrix. Cancer research, 73, 3704–3715.PubMed

146.

Su H, Xu T, Ganapathy S, Shadfan M, Long M, Huang TH, Thompson I, Yuan ZM (2013). Elevated snoRNA biogenesis is essential in breast cancer Oncogene.

147.

Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., et al. (2012). The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer discovery, 2, 401–404.PubMed

148.

Taylor, B. S., Schultz, N., Hieronymus, H., Gopalan, A., Xiao, Y., Carver, B. S., et al. (2010). Integrative genomic profiling of human prostate cancer. Cancer cell, 18, 11–22.PubMedCentralPubMed

149.

Martens-Uzunova, E. S., Jalava, S. E., Dits, N. F., van Leenders, G. J., Moller, S., Trapman, J., et al. (2012). Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer. Oncogene, 31, 978–991.PubMed

150.

Tinker, A. V., Ellard, S., Welch, S., Moens, F., Allo, G., Tsao, M. S., et al. (2013). Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199). Gynecologic oncology, 130, 269–274.PubMed

151.

Gajewski, T. F., Salama, A. K., Niedzwiecki, D., Johnson, J., Linette, G., Bucher, C., et al. (2012). Phase II study of the farnesyltransferase inhibitor R115777 in advanced melanoma (CALGB 500104). Journal of translational medicine, 10, 246.PubMedCentralPubMed

152.

Chaft, J. E., Rusch, V., Ginsberg, M. S., Paik, P. K., Finley, D. J., Kris, M. G., et al. (2013). Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 8, 1084–1090.

153.

Jalali, S., Bhartiya, D., Lalwani, M. K., Sivasubbu, S., & Scaria, V. (2013). Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PloS one, 8, e53823.PubMedCentralPubMed

154.

Luteijn MJ, Ketting RF (2013). PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nature reviews Genetics.

155.

Mei, Y., Clark, D., & Mao, L. (2013). Novel dimensions of piRNAs in cancer. Cancer letters, 336, 46–52.PubMed

156.

Liu LL, Xie N, Sun S, Plymate S, Mostaghel E, Dong X (2013). Mechanisms of the androgen receptor splicing in prostate cancer cells. Oncogene.

157.

Johnsson, P., Ackley, A., Vidarsdottir, L., Lui, W. O., Corcoran, M., Grander, D., et al. (2013). A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells. Nature Structural & Molecular Biology, 20, 440–446.

158.

Volders, P. J., Helsens, K., Wang, X., Menten, B., Martens, L., Gevaert, K., et al. (2013). LNCipedia: a database for annotated human lncRNA transcript sequences and structures. Nucleic acids research, 41, D246–D251.PubMedCentralPubMed

159.

Petrovics, G., Zhang, W., Makarem, M., Street, J. P., Connelly, R., Sun, L., et al. (2004). Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients. Oncogene, 23, 605–611.PubMed

160.

Prensner, J. R., Iyer, M. K., Balbin, O. A., Dhanasekaran, S. M., Cao, Q., Brenner, J. C., et al. (2011). Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression. Nature biotechnology, 29, 742–749.PubMedCentralPubMed

161.

Kalyana-Sundaram, S., Kumar-Sinha, C., Shankar, S., Robinson, D. R., Wu, Y. M., Cao, X., et al. (2012). Expressed pseudogenes in the transcriptional landscape of human cancers. Cell, 149, 1622–1634.PubMedCentralPubMed

162.

Glazko, G. V., Zybailov, B. L., & Rogozin, I. B. (2012). Computational prediction of polycomb-associated long non-coding RNAs. PloS one, 7, e44878.PubMedCentralPubMed

163.

Zielinski, R., & Chi, K. N. (2012). Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin in development for the treatment of prostate cancer. Future Oncology, 8, 1239–1251.PubMed

164.

Rudin, C. M., Marshall, J. L., Huang, C. H., Kindler, H. L., Zhang, C., Kumar, D., et al. (2004). Delivery of a liposomal c-raf-1 antisense oligonucleotide by weekly bolus dosing in patients with advanced solid tumors: a phase I study. Clinical cancer research : an official journal of the American Association for Cancer Research, 10, 7244–7251.

165.

Hong, D. S., Kurzrock, R., Oh, Y., Wheler, J., Naing, A., Brail, L., et al. (2011). A phase 1 dose escalation, pharmacokinetic, and pharmacodynamic evaluation of eIF-4E antisense oligonucleotide LY2275796 in patients with advanced cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 17, 6582–6591.

166.

Yu, B., Mao, Y., Bai, L. Y., Herman, S. E., Wang, X., Ramanunni, A., et al. (2013). Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia. Blood, 121, 136–147.PubMedCentralPubMed

167.

Lippitz, B. E. (2013). Cytokine patterns in patients with cancer: a systematic review. The lancet oncology, 14, e218–e228.PubMed

168.

Tabernero, J., Shapiro, G. I., LoRusso, P. M., Cervantes, A., Schwartz, G. K., Weiss, G. J., et al. (2013). First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer discovery, 3, 406–417.PubMed

169.

Baraniskin, A., Nopel-Dunnebacke, S., Ahrens, M., Jensen, S. G., Zollner, H., Maghnouj, A., et al. (2013). Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma. International journal of cancer (Journal international du cancer), 132, E48–E57.

170.

Watahiki, A., Macfarlane, R. J., Gleave, M. E., Crea, F., Wang, Y., Helgason, C. D., et al. (2013). Plasma miRNAs as biomarkers to identify patients with castration-resistant metastatic prostate cancer. International Journal of Molecular Sciences, 14, 7757–7770.PubMedCentralPubMed

Title: The non-coding transcriptome as a dynamic regulator of cancer metastasis
Authors: Francesco Crea
Pier Luc Clermont
Abhijit Parolia
Yuzhuo Wang
Cheryl D. Helgason
Publication date: 01-03-2014
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-013-9455-3

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