New Insights into P53 Functions Through Its Target MicroRNAs

Overview

Journal J Mol Cell Biol

Publisher Oxford University Press

Specialty Molecular Biology

Date 2014 Apr 18

PMID 24740682

Citations 34

Authors

Jun-Ming Liao

Bo Cao

Xiang Zhou

Hua Lu

Affiliations

Soon will be listed here.

Abstract

The tumor suppressor p53 pathway, whose alterations are highly associated with all types of human cancers, plays an essential role in preventing tumor development and progression mostly through its downstream target genes. Over the last decade, a growing list of p53 microRNA (miRNA) targets has been identified as additional downstream players of this pathway. Further studies of these miRNAs have revealed their more complicated regulations and functions in executing and/or regulating p53 activity. Here, we review the p53 miRNA targets identified thus far, and discuss how they fine-tune p53 stress responses, mediate the crosstalk between p53 and other signaling pathways, and expand the role of p53 in other human diseases in addition to cancers.

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References

Suh S, Chen Y, Zaman M, Hirata H, Yamamura S, Shahryari V . MicroRNA-145 is regulated by DNA methylation and p53 gene mutation in prostate cancer. Carcinogenesis. 2011; 32(5):772-8. PMC: 3086703. DOI: 10.1093/carcin/bgr036. View

Shvarts A, Steegenga W, Riteco N, van Laar T, Dekker P, Bazuine M . MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J. 1996; 15(19):5349-57. PMC: 452278. View

Scarola M, Schoeftner S, Schneider C, Benetti R . miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer Res. 2010; 70(17):6925-33. DOI: 10.1158/0008-5472.CAN-10-0141. View

Lin J, Huo R, Xiao L, Zhu X, Xie J, Sun S . A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol. 2014; 66(1):49-59. DOI: 10.1002/art.38142. View

Maddocks O, Vousden K . Metabolic regulation by p53. J Mol Med (Berl). 2011; 89(3):237-45. PMC: 3043245. DOI: 10.1007/s00109-011-0735-5. View

Guarente L . Sir2 links chromatin silencing, metabolism, and aging. Genes Dev. 2000; 14(9):1021-6. View

Matoba S, Kang J, Patino W, Wragg A, Boehm M, Gavrilova O . p53 regulates mitochondrial respiration. Science. 2006; 312(5780):1650-3. DOI: 10.1126/science.1126863. View

Deshpande S, Putta S, Wang M, Lai J, Bitzer M, Nelson R . Transforming growth factor-β-induced cross talk between p53 and a microRNA in the pathogenesis of diabetic nephropathy. Diabetes. 2013; 62(9):3151-62. PMC: 3749352. DOI: 10.2337/db13-0305. View

Jin L, Hu W, Jiang C, Wang J, Han C, Chu P . MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma. Proc Natl Acad Sci U S A. 2011; 108(38):15840-5. PMC: 3179083. DOI: 10.1073/pnas.1019312108. View

10.

Fornari F, Gramantieri L, Giovannini C, Veronese A, Ferracin M, Sabbioni S . MiR-122/cyclin G1 interaction modulates p53 activity and affects doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2009; 69(14):5761-7. DOI: 10.1158/0008-5472.CAN-08-4797. View

11.

Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J . Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Hum Mol Genet. 2001; 10(18):1915-23. DOI: 10.1093/hmg/10.18.1915. View

12.

Kim H, Roe J, Lee J, Hwang I, Cho E, Youn H . A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH. Biochem Biophys Res Commun. 2012; 418(4):682-8. DOI: 10.1016/j.bbrc.2012.01.077. View

13.

Tian S, Huang S, Wu S, Guo W, Li J, He X . MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region. Biochem Biophys Res Commun. 2010; 396(2):435-9. DOI: 10.1016/j.bbrc.2010.04.112. View

14.

Weeraratne S, Amani V, Neiss A, Teider N, Scott D, Pomeroy S . miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol. 2010; 13(2):165-75. PMC: 3064629. DOI: 10.1093/neuonc/noq179. View

15.

Park S, Lee J, Ha M, Nam J, Kim V . miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol. 2008; 16(1):23-9. DOI: 10.1038/nsmb.1533. View

16.

Bohlig L, Friedrich M, Engeland K . p53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins. Nucleic Acids Res. 2010; 39(2):440-53. PMC: 3025554. DOI: 10.1093/nar/gkq796. View

17.

Migita K, Tanaka F, Yamasaki S, Shibatomi K, Ida H, Kawakami A . Regulation of rheumatoid synoviocyte proliferation by endogenous p53 induction. Clin Exp Immunol. 2001; 126(2):334-8. PMC: 1906196. DOI: 10.1046/j.1365-2249.2001.01677.x. View

18.

Suzuki H, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K . Modulation of microRNA processing by p53. Nature. 2009; 460(7254):529-33. DOI: 10.1038/nature08199. View

19.

Sun Y, Cheung H . p53, proto-oncogene and rheumatoid arthritis. Semin Arthritis Rheum. 2002; 31(5):299-310. DOI: 10.1053/sarh.2002.31550. View

20.

Li J, Donath S, Li Y, Qin D, Prabhakar B, Li P . miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet. 2010; 6(1):e1000795. PMC: 2793031. DOI: 10.1371/journal.pgen.1000795. View