Published in: Cell Volume 75, pp. 1107-1117 (1993):

"Tumor Suppression by RNA from the 3' Untranslated Region of Alpha-Tropomyosin."

Rastinejad F, Conboy MJ, Rando TJ, and Blau, HM, Department of Molecular Pharmacology, School of Medicine, Stanford University, Stanford, CA 94305-5332 USA.



Abstract:

NMU2, a nondifferentiating mutant myogenic cell line, gives rise to rhabdomyosarcomas in mice. We show that constitutive expression of RNA from 0.2 kb of the alpha tropomyosin (Tm) untranslated region (UTR), but not control 3'UTRs, suppresses anchorage-independent growth and tumor formation by NMU2 cells. When beta-galactosidase (beta-gal)-labeled cells were implanted into muscles of adult mouse hindlimbs, Tm 3'UTR expression suppressed the proliferation, invasion, and destruction of muscle tissues characteristic of NMU2. In the rare tumors that developed from Tm 3'UTR transfectants, RNA expression was extinguished. These results suggest that suppression of tumorigenicity is dependent on the continued expression of Tm transcripts lacking a coding region. We conclude that untranslated RNAs can function as regulators (riboregulators) that supress tumor formation.

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85:  Ziober BL, Willson JK, Hymphrey LE, Childress-Fields K, Brattain MG.
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86:  Zeiger MA, Saji M, Caturegli P, Westra WH, Kohn LD, Levine MA.
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Endocrinology. 1996 Dec;137(12):5392-9.
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87:  Horikawa I, Tanaka H, Yuasa Y, Suzuki M, Shimizu M, Oshimura M.
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Exp Cell Res. 1995 Sep;220(1):11-7.
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88:  Kashiwada K, Nishida W, Hayashi K, Ozawa K, Yamanaka Y, Saga H, Yamashita
T, Tohyama M, Shimada S, Sato K, Sobue K.
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J Biol Chem. 1997 Jun 13;272(24):15396-404.
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89:  Lai PF, Mohamed F, Monge JC, Stewart DJ.
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functional characterization of RNA-protein interactions in the 3'UTR.
Cardiovasc Res. 2003 Jul 1;59(1):160-8.
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90:  Yasuda S, Wada S, Arao Y, Kogawa M, Kayama F, Katayama S.
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ribonucleic acid (RNA) and adenylate/uridylate (AU)-rich element binding
proteins (AU-rich RNA-binding factor 1 and Hu antigen R).
Endocrinology. 2004 Apr;145(4):1730-8. Epub 2004 Jan 8.
PMID: 14715706 [PubMed - indexed for MEDLINE]

91:  Peng B, Fleming JB, Breslin T, Grau AM, Fojioka S, Abbruzzese JL, Evans DB,
Ayers D, Wathen K, Wu T, Robertson KD, Chiao PJ.
 Suppression of tumorigenesis and induction of p15(ink4b) by Smad4/DPC4 in human
pancreatic cancer cells.
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92:  Skonier J, Bennett K, Rothwell V, Kosowski S, Plowman G, Wallace P,
Edelhoff S, Disteche C, Neubauer M, Marquardt H, et al.
 beta ig-h3: a transforming growth factor-beta-responsive gene encoding a
secreted protein that inhibits cell attachment in vitro and suppresses the
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DNA Cell Biol. 1994 Jun;13(6):571-84.
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93:  Kim PN, Jonasch E, Mosterman BC, Mier JW, Janssen RA.
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both ras- and MEK-transformed cells without inhibiting the Raf/MEK/ERK signaling
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Cell Growth Differ. 2001 Nov;12(11):543-50.
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94:  Miyado K, Kimura M, Taniguchi S.
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reduction in motility of highly metastatic B16-F10 mouse melanoma cells.
Biochem Biophys Res Commun. 1996 Aug 14;225(2):427-35.
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95:  Platica M, Ivan E, Chen S, Holland JF, Gil J, Mandeli J, Platica O.
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96:  Hales KH, Meredith JE, Storti RV.
 Transcriptional and post-transcriptional regulation of maternal and zygotic
cytoskeletal tropomyosin mRNA during Drosophila development correlates with
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Dev Biol. 1994 Oct;165(2):639-53.
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97:  Shen ZY, Xu LY, Li C, Cai WJ, Shen J, Chen JY, Zeng Y.
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98:  Kerr M, Fischer JE, Purushotham KR, Gao D, Nakagawa Y, Maeda N, Ghanta V,
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99:  Haider SR, Wang W, Kaufman SJ.
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Exp Cell Res. 1994 Feb;210(2):278-86.
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100:  Muthuchamy M, Grupp IL, Grupp G, O'Toole BA, Kier AB, Boivin GP, Neumann
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 Molecular and physiological effects of overexpressing striated muscle
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101:  Carey KA, Segal D, Klein R, Sanigorski A, Walder K, Collier GR,
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 Identification of novel genes expressed during rhabdomyosarcoma differentiation
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102:  Babai F, Royal A.
 Rat myoblastic sarcoma cell lines. A model for the study of invasion,
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103:  Park ES, You SH, Kim H, Kwon OY, Ro HK, Cho BY, Taniguchi SI, Kohn LD,
Shong M.
 Hormone-dependent regulation of intercellular adhesion molecule-1 gene
expression: cloning and analysis of 5'-regulatory region of rat intercellular
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104:  Gross MM, Janiaud P, Stanbridge EJ.
 Effect of retroviral integration on control of expression of a tumor marker in
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105:  Shapiro DN, Jones BG, Shapiro LH, Dias P, Houghton PJ.
 Antisense-mediated reduction in insulin-like growth factor-I receptor
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J Clin Invest. 1994 Sep;94(3):1235-42.
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106:  Kim CJ, Yoshioka N, Tambe Y, Kushima R, Okada Y, Inoue H.
 Periostin is down-regulated in high grade human bladder cancers and suppresses
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107:  Barnes D, Clayton L, Chumbley G, MacLeod AR.
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108:  Carmon Y, Neuman S, Yaffe D.
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109:  Urbancikova M, Grofova M.
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Neoplasma. 1982;29(6):655-60.
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110:  Tremblay JP, Roy B, Goulet M.
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111:  Al-Rubey AK, Chernakova AV, Mosevich TN, Pinchuk VG, Shvemberger IN.
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112:  Hatakeyama S.
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113:  Al-Rubey AK, Chernskova AV, Pinchuk VG, Shvemberger IN.
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114:  Mosevich TN, Shvemberger IN.
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115:  Stepan'ian LI, Shvemberger IN, Vakhtin IuB.
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Tsitologiia. 1980 Jan;22(1):61-7. Russian. No abstract available.
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116:  Stepan'ian LI, Vakhtin IuB.
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117:  Chu-Der OM, Ortwerth BJ.
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Exp Cell Res. 1980 Jul;128(1):159-70. No abstract available.
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118:  Marin G.
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Exp Cell Res. 1980 Jan;125(1):31-6. No abstract available.
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119:  Benecke BJ, Ben-Ze'ev A, Penman S.
 The regulation of RNA metabolism in suspended and reattached
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J Cell Physiol. 1980 May;103(2):247-54. No abstract available.
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120:  MacLeod AR.
 Separation of the mRNAs coding for alpha- and beta-tropomyosin.
FEBS Lett. 1981 Aug 3;130(2):227-9. No abstract available.
PMID: 7286228 [PubMed - indexed for MEDLINE]

121:  Vakhtin IuB.
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Vopr Onkol. 1973;19(4):93-4. Russian. No abstract available.
PMID: 4722831 [PubMed - indexed for MEDLINE]
 



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euchromatin: "the most active portion of the genome within the cell nucleus."