Estrogen Mediated-Activation of miR-191/425 Cluster Modulates Tumorigenicity of Breast Cancer Cells Depending on Estrogen Receptor Status

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MicroRNAs (miRNAs), single-stranded non-coding RNAs, influence myriad biological processes that can contribute to cancer. Although tumor-suppressive and oncogenic functions have been characterized for some miRNAs, the majority of microRNAs have not been investigated for their ability to promote and modulate tumorigenesis. Here, we established that the miR-191/425 cluster is transcriptionally dependent on the host gene, DALRD3, and that the hormone 17β-estradiol (estrogen or E2) controls expression of both miR-191/425 and DALRD3. MiR-191/425 locus characterization revealed that the recruitment of estrogen receptor α (ERα) to the regulatory region of the miR-191/425-DALRD3 unit resulted in the accumulation of miR-191 and miR-425 and subsequent decrease in DALRD3 expression levels. We demonstrated that miR-191 protects ERα positive breast cancer cells from hormone starvation-induced apoptosis through the suppression of tumor-suppressor EGR1. Furthermore, enforced expression of the miR-191/425 cluster in aggressive breast cancer cells altered global gene expression profiles and enabled us to identify important tumor promoting genes, including SATB1, CCND2, and FSCN1, as targets of miR-191 and miR-425. Finally, in vitro and in vivo experiments demonstrated that miR-191 and miR-425 reduced proliferation, impaired tumorigenesis and metastasis, and increased expression of epithelial markers in aggressive breast cancer cells. Our data provide compelling evidence for the transcriptional regulation of the miR-191/425 cluster and for its context-specific biological determinants in breast cancers. Importantly, we demonstrated that the miR-191/425 cluster, by reducing the expression of an extensive network of genes, has a fundamental impact on cancer initiation and progression of breast cancer cells.

Vyšlo v časopise: Estrogen Mediated-Activation of miR-191/425 Cluster Modulates Tumorigenicity of Breast Cancer Cells Depending on Estrogen Receptor Status. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003311
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003311

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Zdroje

1. BartelDP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281–297.

2. ValastyanS, WeinbergRA (2009) MicroRNAs: Crucial multi-tasking components in the complex circuitry of tumor metastasis. Cell cycle 8: 3506–3512.

3. VenturaA, JacksT (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136: 586–591.

4. MendellJT, OlsonEN (2012) MicroRNAs in stress signaling and human disease. Cell 148: 1172–1187.

5. CroceCM (2009) Causes and consequences of microRNA dysregulation in cancer. Nature reviews Genetics 10: 704–714.

6. KasinskiAL, SlackFJ (2011) Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nature reviews Cancer 11: 849–864.

7. IorioMV, FerracinM, LiuCG, VeroneseA, SpizzoR, et al. (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer research 65: 7065–7070.

8. BlenkironC, GoldsteinLD, ThorneNP, SpiteriI, ChinSF, et al. (2007) MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome biology 8: R214.

9. YanLX, HuangXF, ShaoQ, HuangMY, DengL, et al. (2008) MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14: 2348–2360.

10. QianB, KatsarosD, LuL, PretiM, DurandoA, et al. (2009) High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-beta1. Breast cancer research and treatment 117: 131–140.

11. MaL, Teruya-FeldsteinJ, WeinbergRA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449: 682–688.

12. TavazoieSF, AlarconC, OskarssonT, PaduaD, WangQ, et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451: 147–152.

13. ScottGK, GogaA, BhaumikD, BergerCE, SullivanCS, et al. (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. The Journal of biological chemistry 282: 1479–1486.

14. IorioMV, CasaliniP, PiovanC, Di LevaG, MerloA, et al. (2009) microRNA-205 regulates HER3 in human breast cancer. Cancer research 69: 2195–2200.

15. GregoryPA, BertAG, PatersonEL, BarrySC, TsykinA, et al. (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature cell biology 10: 593–601.

16. KorpalM, EllBJ, BuffaFM, IbrahimT, BlancoMA, et al. (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature medicine 17: 1101–1108.

17. AdamsBD, FurneauxH, WhiteBA (2007) The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines. Molecular endocrinology 21: 1132–1147.

18. Bhat-NakshatriP, WangG, CollinsNR, ThomsonMJ, GeistlingerTR, et al. (2009) Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic acids research 37: 4850–4861.

19. CastellanoL, GiamasG, JacobJ, CoombesRC, LucchesiW, et al. (2009) The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response. Proceedings of the National Academy of Sciences of the United States of America 106: 15732–15737.

20. YamagataK, FujiyamaS, ItoS, UedaT, MurataT, et al. (2009) Maturation of microRNA is hormonally regulated by a nuclear receptor. Molecular cell 36: 340–347.

21. Di LevaG, GaspariniP, PiovanC, NgankeuA, GarofaloM, et al. (2010) MicroRNA cluster 221–222 and estrogen receptor alpha interactions in breast cancer. Journal of the National Cancer Institute 102: 706–721.

22. VoliniaS, CalinGA, LiuCG, AmbsS, CimminoA, et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National Academy of Sciences of the United States of America 103: 2257–2261.

23. NakamuraT, CanaaniE, CroceCM (2007) Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing. Proceedings of the National Academy of Sciences of the United States of America 104: 10980–10985.

24. ElyakimE, SitbonE, FaermanA, TabakS, MontiaE, et al. (2010) hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy. Cancer research 70: 8077–8087.

25. HeY, CuiY, WangW, GuJ, GuoS, et al. (2011) Hypomethylation of the hsa-miR-191 locus causes high expression of hsa-mir-191 and promotes the epithelial-to-mesenchymal transition in hepatocellular carcinoma. Neoplasia 13: 841–853.

26. ShiX, SuS, LongJ, MeiB, ChenY (2011) MicroRNA-191 targets N-deacetylase/N-sulfotransferase 1 and promotes cell growth in human gastric carcinoma cell line MGC803. Acta biochimica et biophysica Sinica 43: 849–856.

27. WynendaeleJ, BohnkeA, LeucciE, NielsenSJ, LambertzI, et al. (2010) An illegitimate microRNA target site within the 3′ UTR of MDM4 affects ovarian cancer progression and chemosensitivity. Cancer research 70: 9641–9649.

28. ColamaioM, BorboneE, RussoL, BiancoM, FedericoA, et al. (2011) miR-191 down-regulation plays a role in thyroid follicular tumors through CDK6 targeting. The Journal of clinical endocrinology and metabolism 96: E1915–1924.

29. DoaneAS, DansoM, LalP, DonatonM, ZhangL, et al. (2006) An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene 25: 3994–4008.

30. KlingeCM (2012) miRNAs and estrogen action. Trends in endocrinology and metabolism: TEM 23: 223–233.

31. MutarelliM, CicatielloL, FerraroL, GroberOM, RavoM, et al. (2008) Time-course analyses of genome-wide gene expression data from hormone-responsive breast cancer cells. BMC Bioinformatics 26: S12.

32. PutnikM, ZhaoC, GustafssonJA, Dahlman-WrightK (2012) Global identification of genes regulated by estrogen singaling and demethylation in MCF-7 breats cancer cells. Biochem Biophys Res Commun 426: 26–32.

33. ThielG, CibelliG (2002) Regulation of life and death by the zinc finger transcription factor Egr-1. J Cell Physiol 193: 287–292.

34. KimCG, ChoiBH, SonSW, YiSJ, ShinSY, LeeYH (2007) Tamoxifen-induced activation of p21Waf1/Cip1 gene transcription is mediated by early growth response-1 protein through the JNK and p38 MAP kinase/Elk-1 cascades in MDA-MB-361 breast carcinoma cells. Cell Signal 19: 1290–1300.

35. SuzukiT, InoueA, MikiY, MoriyaT, AkahiraJ, IshidaT, HirakawaH, YamaguchiY, HayashiS, SasanoH (2007) Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor. Endocr Relat Cancer 14: 279–292.

36. Elledge RM, Allred DC (2004) Clinical aspect of estrogen and progesterone receptors. In: Harris JR, Lippman ME, Morrow M, Osborne CK, editors. Disease of the Breast. Philadelphia, PA: Lippincott Williams and Wilkins. pp. 601–617.

37. AllredDC, BrownP, MedinaD (2004) The origin of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer. Breast Cancer Res 6: 240–245.

38. JiangSY, JordanVC (1992) Growth regulation of estrogen receptor-negative breast cancer cells transfected with complementary DNAs for estrogen receptor. J Natl Cancer Inst 84: 580–591.

39. LevensonAS, JordanVC (1994) Transfection of human estrogen receptor (ER) cDNA into ER-negative mammalian cell lines. J Steroid Biochem Mol Biol 51: 229–239.

40. MorrisEJ, MichaudWA, JiJY, MoonNS, RoccoJW, et al. (2006) Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo. PLoS Genet 2: e196 doi:10.1371/journal.pgen.0020196.

41. SourisseauT, GeorgiadisA, TsaparaA, AliRR, PestellR, et al. (2006) Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Molecular and cellular biology 26: 2387–2398.

42. TysonJJ, BaumannWT, ChenC, VerdugoA, TavassolyI, et al. (2011) Dynamic modelling of oestrogen signalling and cell fate in breast cancer cells. Nature reviews Cancer 11: 523–532.

43. FolkmanJ (1990) Endothelial cells and angiogenic growth factors in cancer growth and metastasis. Introduction. Cancer metastasis reviews 9: 171–174.

44. Rodriguez-PinillaSM, SarrioD, HonradoE, HardissonD, CaleroF, et al. (2006) Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas. Clinical cancer research 12: 1533–1539.

45. TavazoieSF, AlarcónC, OskarssonT, PaduaD, WangQ, et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451: 147–152.

46. Al AlwanI, Al-MoamaryM, Al-AttasN, Al KushiA, AlBanyanE, et al. (2011) The progress test as a diagnostic tool for a new PBL curriculum. Education for health 24: 493.

47. KikuchiK, LiX, ZhengY, TakanoY (2011) Invasion of breast cancer cells into collagen matrix requires TGF-alpha and Cdc42 signaling. FEBS letters 585: 286–290.

48. OskarssonT, AcharyyaS, ZhangXH, VanharantaS, TavazoieSF, et al. (2011) Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nature medicine 17: 867–874.

49. HynesNE, StoelzleT (2009) Key signalling nodes in mammary gland development and cancer: Myc. Breast cancer research: BCR 11: 210.

50. HanHJ, RussoJ, KohwiY, Kohwi-ShigematsuT (2008) SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 452: 187–193.

51. KangY, MassagueJ (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118: 277–279.

52. TsukitaS, YamazakiY, KatsunoT, TamuraA (2008) Tight junction-based epithelial microenvironment and cell proliferation. Oncogene 27: 6930–6938.

53. CowinP, RowlandsTM, HatsellSJ (2005) Cadherins and catenins in breast cancer. Current opinion in cell biology 17: 499–508.

54. ZhengGX, RaviA, CalabreseJM, MedeirosLA, KirakO, et al. (2011) A latent pro-survival function for the mir-290–295 cluster in mouse embryonic stem cells. PLoS Genet 7: e1002054 doi:10.1371/journal.pgen.1002054.

55. SoodP, KrekA, ZavolanM, MacinoG, RajewskyN (2006) Cell-type-specific signatures of microRNAs on target mRNA expression. Proceedings of the National Academy of Sciences of the United States of America 103: 2746–2751.

56. SunamiE, ShinozakiM, SimMS, NguyenSL, VuAT, et al. (2008) Estrogen receptor and HER2/neu status affect epigenetic differences of tumor-related genes in primary breast tumors. Breast cancer research: BCR 10: R46.

57. WuZS, WangCQ, XiangR, LiuX, YeS, 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.

58. GromakN, TalottiG, ProudfootNJ, PaganiF (2008) Modulating alternative splicing by cotranscriptional cleavage of nascent intronic RNA. RNA 14: 359–366.

59. YamagataK, FujiyamaS, ItoS, UedaT, MurataT, et al. (2009) Maturation of microRNA is hormonally regulated by a nuclear receptor. Mol Cell 36: 340–347.

60. BjörnströmL, SjöbergM (2005) Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes. Molecular Endocrinology 19: 833–842.

61. MarinoM, GalluzzoP, AscenziP (2006) Estrogen Signaling Multiple Pathways to Impact Gene Transcription. Curr Genomics 7: 497–508.

62. SukhatmeVP, CaoXM, ChangLC, Tsai-MorrisCH, StamenkovichD, et al. (1988) A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53: 37–43.

63. LiuC, RangnekarVM, AdamsonE, MercolaD (1998) Suppression of growth and transformation and induction of apoptosis by EGR-1. Cancer Gene Ther 5: 3–28.

64. LiuC, YaoJ, MercolaD, AdamsonE (2000) The transcription factor EGR-1 directly transactivates the fibronectin gene and enhances attachment of human glioblastoma cell line U251. J Biol Chem 275: 20315–20323.

65. HuangRP, FanY, de BelleI, NiemeyerC, GottardisMM, et al. (1997) Decreased Egr-1 expression in human, mouse and rat mammary cells and tissues correlates with tumor formation. Int J Cancer 72: 102–109.

66. CalogeroA, CuomoL, D'OnofrioM, de GraziaU, SpinsantiP, et al. (1996) Expression of Egr-1 correlates with the transformed phenotype and the type of viral latency in EBV genome positive lymphoid cell lines. Oncogene 13: 2105–2112.

67. AbdulkadirSA, CarboneJM, NaughtonCK, HumphreyPA, CatalonaWJ, et al. (2001) Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma. Hum Pathol 32: 935–939.

68. AhmedMM, VenkatasubbaraoK, FruitwalaSM, et al. (1996) EGR-1 induction is required for maximal radiosensitivity in A375-C6 melanoma cells. J Biol Chem 271: 29231–29237.

69. BaronV, De GregorioG, Krones-HerzigA, et al. (2003) Inhibition of Egr-1 expression reverses transformation of prostate cancer cells in vitro and in vivo. Oncogene 22: 4194–4204.