Selective targeting of KRAS-Mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-Mutant cells

Oncotarget

Volumn 5, Issue 17, 2014, Pages 7635-7650

  Hara, Toshifumi ^a   Jones, Matthew F ^a   Subramanian, Murugan ^a   Li, Xiao Ling ^a   Ou, Oliver ^a   Zhu, Yuelin ^a   Yang, Yuan ^a   Wakefield, Lalage M ^a   Perwez Hussain, S ^a   Gaedcke, Jochen ^b   Ried, Thomas ^a   Luo, Ji ^a   Caplen, Natasha J ^a   Lal, Ashish ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

Author keywords

Colorectal cancer; KRAS; KRAS mutant; miR 126; miRNA

Indexed keywords

MICRORNA 126; KRAS PROTEIN, HUMAN; MICRORNA; MIRN126 MICRORNA, HUMAN; ONCOPROTEIN; RAS PROTEIN;

3' UNTRANSLATED REGION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENICITY; CELL COMPARTMENTALIZATION; CELL MUTANT; CELL SURVIVAL; CELL VIABILITY; CLONOGENESIS; COLORECTAL CANCER CELL LINE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; FEMALE; G1 PHASE CELL CYCLE CHECKPOINT; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE IDENTIFICATION; GENE OVEREXPRESSION; GENE REGULATORY NETWORK; GENE REPRESSION; GENE TARGETING; HUMAN; HUMAN CELL; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; ONCOGENE K RAS; RNA ANALYSIS; TARGET CELL; TRANSCRIPTOMICS; ANIMAL; COLORECTAL TUMOR; FLOW CYTOMETRY; GENETICS; IMMUNOBLOTTING; MUTATION; NUDE MOUSE; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL LINE; XENOGRAFT;

ANIMALS; CELL LINE, TUMOR; COLORECTAL NEOPLASMS; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HETEROGRAFTS; HUMANS; IMMUNOBLOTTING; MICE; MICE, NUDE; MICRORNAS; MUTATION; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84907484056     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2284     Document Type: Article

References (71)

1. Friedman RC, Farh KK, Burge CB and Bartel DP. Most mammalian mrnas are conserved targets of micrornas. Genome Res. 2009; 19(1):92-105.
2. Ameres SL and Zamore PD. Diversifying microrna sequence and function. Nat Rev Mol Cell Biol. 2013; 14(8):475-488.
3. Tay Y, Zhang J, Thomson AM, Lim B and Rigoutsos I. Micrornas to nanog, oct4 and sox2 coding regions modulate embryonic stem cell differentiation. Nature. 2008; 455(7216):1124-1128.
4. Rigoutsos I. New tricks for animal micrornas: Targeting of amino acid coding regions at conserved and nonconserved sites. Cancer Res. 2009; 69(8):3245-3248.
5. Lal A, Navarro F, Maher CA, Maliszewski LE, Yan N, O'Day E, Chowdhury D, Dykxhoorn DM, Tsai P, Hofmann O, Becker KG, Gorospe M, Hide W and Lieberman J. Mir-24 inhibits cell proliferation by targeting e2f2, myc, and other cell-cycle genes via binding to "seedless" 3'utr microrna recognition elements. Mol Cell. 2009; 35(5):610-625.
6. Loeb GB, Khan AA, Canner D, Hiatt JB, Shendure J, Darnell RB, Leslie CS and Rudensky AY. Transcriptome-wide mir-155 binding map reveals widespread noncanonical microrna targeting. Mol Cell. 2012; 48(5):760-770.
7. Garzon R, Marcucci G and Croce CM. Targeting micrornas in cancer: Rationale, strategies and challenges. Nat Rev Drug Discov. 2010; 9(10):775-789.
8. Croce CM. Causes and consequences of microrna dysregulation in cancer. Nat Rev Genet. 2009; 10(10):704-714.
9. Kasinski AL and Slack FJ. Epigenetics and genetics. Micrornas en route to the clinic: Progress in validating and targeting micrornas for cancer therapy. Nat Rev Cancer. 2011; 11(12):849-864.
10. Medina PP and Slack FJ. Micrornas and cancer: An overview. Cell Cycle. 2008; 7(16):2485-2492.
11. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B and Lieberman J. Mir-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One. 2009; 4(9):e7181.
12. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celia-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia BA, Ragoussis J, Amadori D, Harris AL, et al. Direct targeting of sec23a by mir-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 2011; 17(9):1101-1108.
13. Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaelian I and Mazoyer S. Down-regulation of brca1 expression by mir-146a and mir-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med. 2011; 3(5):279-290.
14. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, et al. A microrna expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-2261.
15. Han YC, Park CY, Bhagat G, Zhang J, Wang Y, Fan JB, Liu M, Zou Y, Weissman IL and Gu H. Microrna-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia. J Exp Med. 2010; 207(3):475-489.
16. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, et al. Microrna-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3a and 3b. Proc Natl Acad Sci U S A. 2007; 104(40):15805-15810.
17. Ratner E, Lu L, Boeke M, Barnett R, Nallur S, Chin LJ, Pelletier C, Blitzblau R, Tassi R, Paranjape T, Hui P, Godwin AK, Yu H, Risch H, Rutherford T, Schwartz P, et al. A kras-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res. 2010; 70(16):6509-6515.
18. Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, et al. A snp in a let-7 microrna complementary site in the kras 3' untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008; 68(20):8535-8540.
19. Mayr C and Bartel DP. Widespread shortening of 3'utrs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell. 2009; 138(4):673-684.
20. Kedde M, van Kouwenhove M, Zwart W, Oude Vrielink JA, Elkon R and Agami R. A pumilio-induced rna structure switch in p27-3' utr controls mir-221 and mir-222 accessibility. Nat Cell Biol. 2010; 12(10):1014-1020.
21. Pylayeva-Gupta Y, Grabocka E and Bar-Sagi D. Ras oncogenes: Weaving a tumorigenic web. Nat Rev Cancer. 2011; 11(11):761-774.
22. Bos JL. Ras oncogenes in human cancer: A review. Cancer Res. 1989; 49(17):4682-4689.
23. Karnoub AE and Weinberg RA. Ras oncogenes: Split personalities. Nat Rev Mol Cell Biol. 2008; 9(7):517-531.
24. Chitale D, Gong Y, Taylor BS, Broderick S, Brennan C, Somwar R, Golas B, Wang L, Motoi N, Szoke J, Reinersman JM, Major J, Sander C, Seshan VE, Zakowski MF, Rusch V, et al. An integrated genomic analysis of lung cancer reveals loss of dusp4 in egfr-mutant tumors. Oncogene. 2009; 28(31):2773-2783.
25. Tomida S, Takeuchi T, Shimada Y, Arima C, Matsuo K, Mitsudomi T, Yatabe Y and Takahashi T. Relapse-related molecular signature in lung adenocarcinomas identifies patients with dismal prognosis. J Clin Oncol. 2009; 27(17):2793-2799.
26. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong KK and Elledge SJ. A genome-wide rnai screen identifies multiple synthetic lethal interactions with the ras oncogene. Cell. 2009; 137(5):835-848.
27. Luo J, Solimini NL and Elledge SJ. Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell. 2009; 136(5):823-837.
28. Scholl C, Frohling S, Dunn IF, Schinzel AC, Barbie DA, Kim SY, Silver SJ, Tamayo P, Wadlow RC, Ramaswamy S, Dohner K, Bullinger L, Sandy P, Boehm JS, Root DE, Jacks T, et al. Synthetic lethal interaction between oncogenic kras dependency and stk33 suppression in human cancer cells. Cell. 2009; 137(5):821-834.
29. Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, Frohling S, Chan EM, Sos ML, Michel K, Mermel C, Silver SJ, et al. Systematic rna interference reveals that oncogenic kras-driven cancers require tbk1. Nature. 2009; 462(7269):108-112.
30. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, Schmidt K, Willson JK, Markowitz S, Zhou S, Diaz LA, Jr., Velculescu VE, Lengauer C, Kinzler KW, Vogelstein B and Papadopoulos N. Glucose deprivation contributes to the development of kras pathway mutations in tumor cells. Science. 2009; 325(5947):1555-1559.
31. Li XL, Hara T, Choi Y, Subramanian M, Francis P, Bilke S, Walker RL, Pineda M, Zhu Y, Yang Y, Luo J, Wakefield LM, Brabletz T, Park BH, Sharma S, Chowdhury D, et al. A p21-zeb1 complex inhibits epithelial-mesenchymal transition through the microrna 183-96-182 cluster. Mol Cell Biol. 2014; 34(3):533-550.
32. Han Z, Yang Q, Liu B, Wu J, Li Y, Yang C and Jiang Y. Microrna-622 functions as a tumor suppressor by targeting k-ras and enhancing the anticarcinogenic effect of resveratrol. Carcinogenesis. 2012; 33(1):131-139.
33. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C and Schultz N. The cbio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-404.
34. Thomson DW, Bracken CP, Szubert JM and Goodall GJ. On measuring mirnas after transient transfection of mimics or antisense inhibitors. PLoS One. 2013; 8(1):e55214.
35. Gallaher AM, Das S, Xiao Z, Andresson T, Kieffer-Kwon P, Happel C and Ziegelbauer J. Proteomic screening of human targets of viral micrornas reveals functions associated with immune evasion and angiogenesis. PLoS Pathog. 2013; 9(9):e1003584.
36. Subramanian M, Francis P, Bilke S, Li XL, Hara T, Lu X, Jones MF, Walker RL, Zhu Y, Pineda M, Lee C, Varanasi L, Yang Y, Martinez LA, Luo J, Ambs S, et al. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis. Oncogene. 2014.
37. Weng MT, Lee JH, Wei SC, Li Q, Shahamatdar S, Hsu D, Schetter AJ, Swatkoski S, Mannan P, Garfield S, Gucek M, Kim MK, Annunziata CM, Creighton CJ, Emanuele MJ, Harris CC, et al. Evolutionarily conserved protein erh controls cenp-e mrna splicing and is required for the survival of kras mutant cancer cells. Proc Natl Acad Sci U S A. 2012; 109(52):E3659-3667.
38. Lal A, Kim HH, Abdelmohsen K, Kuwano Y, Pullmann R, Jr., Srikantan S, Subrahmanyam R, Martindale JL, Yang X, Ahmed F, Navarro F, Dykxhoorn D, Lieberman J and Gorospe M. P16(ink4a) translation suppressed by mir-24. PLoS One. 2008; 3(3):e1864.
39. Vasudevan S, Tong Y and Steitz JA. Switching from repression to activation: Micrornas can up-regulate translation. Science. 2007; 318(5858):1931-1934.
40. Forman JJ, Legesse-Miller A and Coller HA. A search for conserved sequences in coding regions reveals that the let-7 microrna targets dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008; 105(39):14879-14884.
41. Abdelmohsen K, Srikantan S, Kuwano Y and Gorospe M. Mir-519 reduces cell proliferation by lowering rna-binding protein hur levels. Proc Natl Acad Sci U S A. 2008; 105(51):20297-20302.
42. Baek D, Villen J, Shin C, Camargo FD, Gygi SP and Bartel DP. The impact of micrornas on protein output. Nature. 2008; 455(7209):64-71.
43. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R and Rajewsky N. Widespread changes in protein synthesis induced by micrornas. Nature. 2008; 455(7209):58-63.
44. Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A and Mendell JT. Transactivation of mir-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007; 26(5):745-752.
45. Miranda KC, Huynh T, Tay Y, Ang YS, Tam WL, Thomson AM, Lim B and Rigoutsos I. A pattern-based method for the identification of microrna binding sites and their corresponding heteroduplexes. Cell. 2006; 126(6):1203-1217.
46. Loher P and Rigoutsos I. Interactive exploration of rna22 microrna target predictions. Bioinformatics. 2012; 28(24):3322-3323.
47. Kruger J and Rehmsmeier M. Rnahybrid: Microrna target prediction easy, fast and flexible. Nucleic Acids Res. 2006; 34(Web Server issue):W451-454.
48. Zhang J, Zhang Z, Zhang DY, Zhu J, Zhang T and Wang C. Microrna 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the pik3r2-pi3k/akt signalling pathway. PLoS One. 2013; 8(12):e83294.
49. Zhu N, Zhang D, Xie H, Zhou Z, Chen H, Hu T, Bai Y, Shen Y, Yuan W, Jing Q and Qin Y. Endothelial-specific intron-derived mir-126 is down-regulated in human breast cancer and targets both vegfa and pik3r2. Mol Cell Biochem. 2011; 351(1-2):157-164.
50. Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY and Srivastava D. Mir-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008; 15(2):272-284.
51. Guo C, Sah JF, Beard L, Willson JK, Markowitz SD and Guda K. The noncoding rna, mir-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer. 2008; 47(11):939-946.
52. Kuhnert F, Mancuso MR, Hampton J, Stankunas K, Asano T, Chen CZ and Kuo CJ. Attribution of vascular phenotypes of the murine egfl7 locus to the microrna mir-126. Development. 2008; 135(24):3989-3993.
53. Zhang Y, Wang X, Xu B, Wang B, Wang Z, Liang Y, Zhou J, Hu J and Jiang B. Epigenetic silencing of mir-126 contributes to tumor invasion and angiogenesis in colorectal cancer. Oncol Rep. 2013; 30(4):1976-1984.
54. Liu Y, Zhou Y, Feng X, Yang P, Yang J, An P, Wang H, Ye S, Yu C, He Y and Luo H. Low expression of microrna-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer. 2014; 53(4):358-365.
55. Ebrahimi F, Gopalan V, Smith RA and Lam AK. Mir-126 in human cancers: Clinical roles and current perspectives. Exp Mol Pathol. 2014; 96(1):98-107.
56. Hamada S, Satoh K, Fujibuchi W, Hirota M, Kanno A, Unno J, Masamune A, Kikuta K, Kume K and Shimosegawa T. Mir-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of adam9. Mol Cancer Res. 2012; 10(1):3-10.
57. Zhou J, Li YS, Nguyen P, Wang KC, Weiss A, Kuo YC, Chiu JJ, Shyy JY and Chien S. Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microrna-126: Role of shear stress. Circ Res. 2013; 113(1):40-51.
58. Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O'Neill SJ, McElvaney NG and Greene CM. Mir-126 is downregulated in cystic fibrosis airway epithelial cells and regulates tom1 expression. J Immunol. 2010; 184(4):1702-1709.
59. Miko E, Margitai Z, Czimmerer Z, Varkonyi I, Dezso B, Lanyi A, Bacso Z and Scholtz B. Mir-126 inhibits proliferation of small cell lung cancer cells by targeting slc7a5. FEBS Lett. 2011; 585(8):1191-1196.
60. Yang C, Hou C, Zhang H, Wang D, Ma Y, Zhang Y, Xu X, Bi Z and Geng S. Mir-126 functions as a tumor suppressor in osteosarcoma by targeting sox2. Int J Mol Sci. 2014; 15(1):423-437.
61. Shen WF, Hu YL, Uttarwar L, Passegue E and Largman C. Microrna-126 regulates hoxa9 by binding to the homeobox. Mol Cell Biol. 2008; 28(14):4609-4619.
62. Jiao LR, Frampton AE, Jacob J, Pellegrino L, Krell J, Giamas G, Tsim N, Vlavianos P, Cohen P, Ahmad R, Keller A, Habib NA, Stebbing J and Castellano L. Micrornas targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors. PLoS One. 2012; 7(2):e32068.
63. Kim HH, Kuwano Y, Srikantan S, Lee EK, Martindale JL and Gorospe M. Hur recruits let-7/risc to repress c-myc expression. Genes Dev. 2009; 23(15):1743-1748.
64. Miles WO, Tschop K, Herr A, Ji JY and Dyson NJ. Pumilio facilitates mirna regulation of the e2f3 oncogene. Genes Dev. 2012; 26(4):356-368.
65. Kedde M, Strasser MJ, Boldajipour B, Oude Vrielink JA, Slanchev K, le Sage C, Nagel R, Voorhoeve PM, van Duijse J, Orom UA, Lund AH, Perrakis A, Raz E and Agami R. Rna-binding protein dnd1 inhibits microrna access to target mrna. Cell. 2007; 131(7):1273-1286.
66. Okada N, Lin CP, Ribeiro MC, Biton A, Lai G, He X, Bu P, Vogel H, Jablons DM, Keller AC, Wilkinson JE, He B, Speed TP and He L. A positive feedback between p53 and mir-34 mirnas mediates tumor suppression. Genes Dev. 2014; 28(5):438-450.
67. Nam JW, Rissland OS, Koppstein D, Abreu-Goodger C, Jan CH, Agarwal V, Yildirim MA, Rodriguez A and Bartel DP. Global analyses of the effect of different cellular contexts on microrna targeting. Mol Cell. 2014; 53(6):1031-1043.
68. Guo H, Ingolia NT, Weissman JS and Bartel DP. Mammalian micrornas predominantly act to decrease target mrna levels. Nature. 2010; 466(7308):835-840.
69. Djuranovic S, Nahvi A and Green R. Mirna-mediated gene silencing by translational repression followed by mrna deadenylation and decay. Science. 2012; 336(6078):237-240.
70. Kleijnen MF, Alarcon RM and Howley PM. The ubiquitin-associated domain of hplic-2 interacts with the proteasome. Mol Biol Cell. 2003; 14(9):3868-3875.
71. Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, et al. Mutations in ubqln2 cause dominant x-linked juvenile and adult-onset als and als/dementia. Nature. 2011; 477(7363):211-215.