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MicroRNA-181a – a tale of discrepancies

  • Aliaa M. Seoudi (a1), Yasmine A. Lashine (a1) and Ahmed I. Abdelaziz (a1)

MicroRNAs (miRNAs) are short noncoding RNAs that act as post-transcriptional regulators. The low complementarity required between the sequences of a miRNA and its target mRNA enables a single miRNA to act on a large range of targets. Thus miRNAs have an intersecting complex effect that spans a multiplicity of pathways and processes. In this review, the different roles of a vital miRNA, miR-181a, in physiological and pathological developments are collated in an attempt to highlight the intersections of such processes and to show how the deregulation of miR-181a could in one context drive malignancy, whereas in another it can lead to autoimmunity. Such deregulation could be related to the faulty levels of one of its own targets, p53, which was recently reported to control an array of miRNAs, one of which is miR-181a. This sheds light on a hidden loop of chaos behind chronic diseases such as autoimmunity and cancer.

Corresponding author
*Corresponding author: Ahmed I. Abdelaziz, The German University in Cairo – GUC, New Cairo City – Main Entrance of Al Tagamoa Al Khames, 11835 Cairo, Egypt. E-mail:
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

2 B.P. Lewis (2003) Prediction of Mammalian MicroRNA Targets. Cell 115, 787-798

3 G.A. Calin and C.M. Croce (2006) MicroRNA signatures in human cancers. Natures Reviews Cancer 6, 857-866

5 L.P. Lim (2005) Microarray analysis shows that some microRNAs downregulate a large number of target mRNAs. Nature 433, 769-773

6 S. Huang (2010) MicroRNA-181a modulates gene expression of zinc finger family members by directly targeting their coding regions. Nucleic Acids Research 38, 7211-7218.

7 Z. Chng (2010) SIP1 mediates cell-fate decisions between neuroectoderm and mesendoderm in human pluripotent stem cells. Cell Stem Cell 6, 59-70

8 L. Shaw , P.A. Johnson and S.J. Kimber (2010) Gene expression profiling of the developing mouse kidney and embryo. In Vitro Cellular and Developmental Biology. Animal 46, 155-165

9 E. Seuntjens (2009) Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors. Nature Neuroscience 12, 1373-1380

10 A. Yoshimoto (2005) Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation. Development 132, 4437-4448

11 H. Peinado , D. Olmeda and A. Cano (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Reviews Cancer 7, 415-428

12 L.R. Saunders (2010) miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues. Aging (Albany NY) 2, 415-431

14 J. Ji (2009) Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells. Hepatology 50, 472-480

15 Q. Pan (2007) The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression. Molecular Human Reproduction 13, 797-806

16 Y.G. Li (2009) Knockdown of microRNA-181 by lentivirus mediated siRNA expression vector decreases the arrhythmogenic effect of skeletal myoblast transplantation in rat with myocardial infarction. Microvascular Research 78, 393-404

17 A. Safdar (2009) miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6J male mice. PLoS One 4, e5610

18 J. Kazenwadel , M.Z. Michael and N.L. Harvey (2010) Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood 116, 2395-2401

19 C.Z. Chen (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83-86

20 S.H. Ramkissoon (2006) Hematopoietic-specific microRNA expression in human cells. Leukemia Research 30, 643-647

21 H. Okada , G. Kohanbash and M.T. Lotze (2010) MicroRNAs in immune regulation – opportunities for cancer immunotherapy. International Journal of Biochemistry and Cell Biology 42, 1256-1261

22 P.J. Ebert (2009) An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nature Immunology 10, 1162-1169

23 J.R. Neilson (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes and Development 21, 578-589

24 G. Liu (2008) Pre-miRNA loop nucleotides control the distinct activities of mir-181a-1 and mir-181c in early T cell development. PLoS One 3, e3592

25 Q.J. Li (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129, 147-161

26 B.N. Dittel (1999) Cross-antagonism of a T cell clone expressing two distinct T cell receptors. Immunity 11, 289-298

27 I. Stefanova (2003) TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nature Immunology 4, 248-254

28 G. Altan-Bonnet and R.N. Germain (2005) Modeling T cell antigen discrimination based on feedback control of digital ERK responses. PLoS Biology 3, e356

29 M.L. Choong , H.H. Yang and I. McNiece (2007) MicroRNA expression profiling during human cord blood-derived CD34 cell erythropoiesis. Experimental Hematology 35, 551-564

30 W. Gao (2011) MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. Journal of Cancer Research and Clinical Oncology 137, 557-566

31 K.H. Shin (2011) miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras. Biochemical and Biophysical Research Communications 404, 896-902

32 C. Caulin (2004) Inducible activation of oncogenic K-ras results in tumor formation in the oral cavity. Cancer Research 64, 5054-5058

33 W. Gao (2010) Deregulated expression of miR-21, miR-143 and miR-181a in non small cell lung cancer is related to clinicopathologic characteristics or patient prognosis. Biomedicine and Pharmacotherapy 64, 399-408

34 A.M. Cheng (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Research 33, 1290-1297

35 J. Fei (2008) Inhibitory effects of anti-miRNA oligonucleotides (AMOs) on A549 cell growth. Journal of Drug Targeting 16, 688-693

36 L. Galluzzi (2010) miR-181a and miR-630 regulate cisplatin-induced cancer cell death. Cancer Research 70, 1793-1803

37 S.A. Ciafre (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochemical and Biophysical Research Communications 334, 1351-1358

38 L. Shi (2008) hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Research 1236, 185-193

40 A.I. Wald (2010) Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head and Neck 33, 504-512

41 T.E. Miller (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. Journal of Biological Chemistry 283, 29897-29903

42 Y. Wang (2010) Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene 30, 1470-1480

43 G. Maillot (2009) Widespread estrogen-dependent repression of micrornas involved in breast tumor cell growth. Cancer Research 69, 8332-8340

45 A. Pons (2009) Hematopoiesis-related microRNA expression in myelodysplastic syndromes. Leukemia and Lymphoma 50, 1854-1859

46 Y. Wang (2010) MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cells, Molecules and Diseases 44, 191-197

47 E.I. Zimmerman (2010) Lyn kinase-dependent regulation of miR181 and Mcl-1 expression: implications for drug resistance in myelogenous leukemia. Molecular Pharmacology 78, 811-817

48 F. Pichiorri (2008) MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proceedings of the National Academy of Sciences of the United States of America 105, 12885-12890

49 T. Lwin (2010) Follicular dendritic cell-dependent drug resistance of non-Hodgkin lymphoma involves cell adhesion-mediated Bim down-regulation through induction of microRNA-181a. Blood 116, 5228-5236

50 M. Mortarino (2010) Identification of suitable endogenous controls and differentially expressed microRNAs in canine fresh-frozen and FFPE lymphoma samples. Leukemia Research 34, 1070-1077

51 S. Marton (2008) Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis. Leukemia 22, 330-338

52 R. Visone (2009) Karyotype-specific microRNA signature in chronic lymphocytic leukemia. Blood 114, 3872-3879

53 G.A. Calin , Y. Pekarsky and C.M. Croce (2007) The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia. Best Practice and Research. Clinical Haematology 20, 425-437

54 C.P. Pallasch (2009) miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia. Blood 114, 3255-3264

55 S. Pizzimenti (2009) MicroRNA expression changes during human leukemic HL-60 cell differentiation induced by 4-hydroxynonenal, a product of lipid peroxidation. Free Radical Biology and Medicine 46, 282-288

57 X. Wang (2009) MicroRNAs181 regulate the expression of p27Kip1 in human myeloid leukemia cells induced to differentiate by 1,25-dihydroxyvitamin D3. Cell Cycle 8, 736-741

58 C.G. Vinuesa , R.J. Rigby and D. Yu (2009) Logic and extent of miRNA-mediated control of autoimmune gene expression. International Review of Immunology 28, 112-138

59 J.L. Te (2010) Identification of unique microRNA signature associated with lupus nephritis. PLoS One 5, e10344

60 L. Boominathan (2010) The tumor suppressors p53, p63, and p73 are regulators of microRNA processing complex. PLoS One 5, e10615

61 V. Tarasov (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6, 1586-1593

62 J. Tsang , J. Zhu and A. van Oudenaarden (2007) MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Molecular Cell 26, 753-767

64 G. Fontanini (1994) Human non-small cell lung cancer: p53 protein accumulation is an early event and persists during metastatic progression. Journal of Pathology 174, 23-31

65 M.W. Gross (2005) Expression of p53 and p21 in primary glioblastomas. Strahlentherapie und Onkologie 181, 164-171

66 Z.A. El-Sayed , D.H. Farag and S. Eissa (2003) Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological diseases. Pediatric Allergy and Immunology 14, 229-233

67 M. Kataoka (2000) Down-regulation of bcl-2 is associated with p16INK4-mediated apoptosis in non-small cell lung cancer cells. Oncogene 19, 1589-1595

70 O. Markovic (2007) The expression of p53 protein in patients with multiple myeloma. Srpski arhiv za Celokupno lekarstvo 135, 43-47

72 S. Bovenkerk , N. Lanciloti and N. Chandar (2003) Induction of p53 expression and function by estrogen in osteoblasts. Calcified Tissue International 73, 274-280

73 C. Esau (2004) MicroRNA-143 regulates adipocyte differentiation. Journal of Biological Chemistry 279, 52361-52365

74 J. Stenvang (2008) The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Seminars in Cancer Biology 18, 89-102

75 I. Naguibneva (2006) An LNA-based loss-of-function assay for micro-RNAs. Biomedicine and Pharmacotherapy 60, 633-638

76 U.A. Orom , S. Kauppinen and A.H. Lund (2006) LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene 372, 137-141

77 C. Esau (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metabolism 3, 87-98

78 J. Krutzfeldt (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438, 685-689

79 M.S. Ebert , J.R. Neilson and P.A. Sharp (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nature Methods 4, 721-726

80 W.Y. Choi , A.J. Giraldez and A.F. Schier (2007) Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 318, 271-274

81 J. Xiao (2007) Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4. Journal of Cellular Physiology 212, 285-292

82 Z. Hua (2006) MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1, e116

83 C.N. Landen Jr. (2005) Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Research 65, 6910-6918

84 C. Lu (2010) Regulation of tumor angiogenesis by EZH2. Cancer Cell 18, 185-197

85 M.M. Shahzad (2011) Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles. Neoplasia 13, 309-319

86 J. Yamamoto (2003) Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ. Human Pathology 34, 1108-1115

90 S.Y. Sun (2001) Overexpression of BCL2 blocks TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. Biochemical and Biophysical Research Communications 280, 788-797

93 O. Gautschi (2007) Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer 55, 1-14

94 T. Elsir (2010) Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas. Journal of Neuropathology and Experimental Neurology 69, 129-138

95 A.H. Stegh (2010) Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor. Genes and Development 24, 2194-2204

97 R. Piva (1997) p27/kip1 expression in human astrocytic gliomas. Neuroscience Letters 234, 127-130

98 J. Andre (2007) Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus. Lupus 16, 95-100

99 D. Gomez-Martin Quantitative and functional profiles of CD4+ lymphocyte subsets in systemic lupus erythematosus patients with lymphopenia. Clinical and Experimental Immunology 164, 17-25

100 S. Hillion (2007) Interleukin-6 is responsible for aberrant B-cell receptor-mediated regulation of RAG expression in systemic lupus erythematosus. Immunology 122, 371-380

101 T. Akimoto (1998) Effect of radiation on the expression of E-cadherin and alpha-catenin and invasive capacity in human lung cancer cell line in vitro. International Journal of Radiative Oncology, Biology, Physics 41, 1171-1176

103 Q. Cheng (2000) Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-kappaB inhibition. Oncogene 19, 4936-4940

104 Q. Niu (2011) Cord blood-derived cytokine-induced killer cells biotherapy combined with second-line chemotherapy in the treatment of advanced solid malignancies. International Immunopharmacology 11, 449-456

105 S.Y. Shin (2004) Implication of Egr-1 in trifluoperazine-induced growth inhibition in human U87MG glioma cells. Experimental and Molecular Medicine 36, 380-386

107 M. Ebrahimi (2008) Decreased expression of the p63 related proteins beta-catenin, E-cadherin and EGFR in oral lichen planus. Oral Oncology 44, 634-638

108 J.A. Akervall (1997) Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression. Cancer 79, 380-389

110 L.E. Van den Hove (1998) Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. Leukemia Research 22, 175-184

111 J.W. Said (2001) TCL1 oncogene expression in B cell subsets from lymphoid hyperplasia and distinct classes of B cell lymphoma. Laboratory Investigation 81, 555-564

112 J. Shaughnessy (2005) Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma. Hematology 10, 117-126

113 X. Liu and R. Feng (2010) Inhibition of epithelial to mesenchymal transition in metastatic breast carcinoma cells by c-Src suppression. Acta Biochimica et Biophysica Sinica 42, 496-501

115 R.M. Zwijsen (1996) Cyclin D1 triggers autonomous growth of breast cancer cells by governing cell cycle exit. Molecular and Cellular Biology 16, 2554-2560

116 T. Hu (2008) Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis. Cancer Research 68, 6533-6540

118 H. Zhao (2009) The c-myb proto-oncogene and microRNA-15a comprise an active autoregulatory feedback loop in human hematopoietic cells. Blood 113, 505-516

119 F. Petrocca (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13, 272-286

E. Tili (2007) miRNAs and their potential for use against cancer and other diseases. Future Oncology 3, 521-537

X. Zhang and X. Lu (2011) Posttranscriptional regulation of miRNAs in the DNA damage response. RNA Biology 8, 960-963

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