RAS-MAPK pathway epigenetic activation in cancer: MiRNAs in action

Oncotarget

Volumn 7, Issue 25, 2016, Pages 38892-38907

  Masliah Planchon, Julien ^a,b   Garinet, Simon ^c   Pasmant, Eric ^c,d  

^a INSTITUT CURIE   (France)

^b INSTITUT CURIE   (France)

^c Faculté des Sciences Pharmaceutiques et Biologiques ^*  (France)

^d UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Cancer; Epigenetics; MicroRNAs; RAS MAPK pathway

Indexed keywords

A RAF KINASE; B RAF KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; K RAS PROTEIN; MICRORNA; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; PROTEIN RAF1; PROTEIN SPRED1; PROTEIN TYROSINE PHOSPHATASE SHP 2; RAS P21 PROTEIN ACTIVATOR GTPASE ACTIVATING PROTEIN 1; RAS PROTEIN; SOS PROTEIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CANCER GROWTH; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; EPIGENETICS; GENE ACTIVATION; HUMAN; NEOPLASM; NF1 GENE; NONHUMAN; ONCOGENE H RAS; ONCOGENE N RAS; ONCOGENE RAS; SIGNAL TRANSDUCTION; SOMATIC MUTATION; ANIMAL; CELL TRANSFORMATION; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; MAPK SIGNALING; METABOLISM; MOUSE; MUTATION; TREATMENT OUTCOME;

ANIMALS; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; CELL TRANSFORMATION, NEOPLASTIC; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MAP KINASE SIGNALING SYSTEM; MICE; MICRORNAS; MUTATION; NEOPLASMS; RAS PROTEINS; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84978076696     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6476     Document Type: Article

References (128)

1. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003; 3:11-22.
2. Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, Chang DK, Cowley MJ, Gardiner BB, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature. 2012; 491:399-405.
3. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, et al. A landscape of driver mutations in melanoma. Cell. 2012; 150:251-63.
4. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012; 481:157-63.
5. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012; 487:330-7.
6. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012; 150:1107-20.
7. Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG, Ladanyi M, Riely GJ. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011; 29:2046-51.
8. De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, Helin K, Hornick JL, Mautner V, Kehrer-Sawatzki H, Clapp W, Bradner J, Vidaud M, et al. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014; 514:247-51.
9. Fabbri M, Calore F, Paone A, Galli R, Calin GA. Epigenetic regulation of miRNAs in cancer. Adv Exp Med Biol. 2013; 754:137-48.
10. Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, Willoughby CE. Mutation altering the miR-184 seed region causes familial keratoconus with cataract. Am J Hum Genet. 2011; 89:628-33.
11. Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, van Dongen S, Abreu-Goodger C, Piipari M, Redshaw N, Dalmay T, Moreno-Pelayo MA, Enright AJ, et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet. 2009; 41:614-8.
12. de Pontual L, Yao E, Callier P, Faivre L, Drouin V, Cariou S, Van Haeringen A, Geneviève D, Goldenberg A, Oufadem M, Manouvrier S, Munnich A, Vidigal JA, et al. Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in humans. Nat Genet. 2011; 43:1026-30.
13. Bueno MJ, Malumbres M. MicroRNAs and the cell cycle. Biochim Biophys Acta. 2011; 1812:592-601.
14. Di Leva G, Garofalo M, Croce CM. MicroRNAs in cancer. Annu Rev Pathol. 2014; 9:287-314.
15. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009; 11:228-34.
16. Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, et al. DICER1 mutations in familial pleuropulmonary blastoma. Science. 2009; 325:965.
17. Foulkes WD, Priest JR, Duchaine TF. DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer. 2014; 14:662-72.
18. Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, Urbauer D, Pennacchio LA, Cheng JF, Nick AM, Deavers MT, Mourad-Zeidan A, Wang H, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008; 359:2641-50.
19. Rakheja D, Chen KS, Liu Y, Shukla AA, Schmid V, Chang TC, Khokhar S, Wickiser JE, Karandikar NJ, Malter JS, Mendell JT, Amatruda JF. Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat Commun. 2014; 2:4802.
20. Tokumaru S, Suzuki M, Yamada H, Nagino M, Takahashi T. let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis. 2008; 29:2073-7.
21. Weiss GJ, Bemis LT, Nakajima E, Sugita M, Birks DK, Robinson WA, Varella-Garcia M, Bunn PA, Haney J, Helfrich BA, Kato H, Hirsch FR, Franklin WA. EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann Oncol. 2008; 19:1053-9.
22. Cho WCS, Chow ASC, Au JSK. MiR-145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1. RNA Biol. 2011; 8:125-31.
23. Mataki H, Seki N, Chiyomaru T, Enokida H, Goto Y, Kumamoto T, Machida K, Mizuno K, Nakagawa M, Inoue H. Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma. Int J Oncol. 2015; 46:1039-50.
24. Rao SAM, Arimappamagan A, Pandey P, Santosh V, Hegde AS, Chandramouli BA, Somasundaram K. miR-219-5p inhibits receptor tyrosine kinase pathway by targeting EGFR in glioblastoma. PloS One. 2013; 8:e63164.
25. Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S, Purow B. microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res. 2008; 68:3566-72.
26. Katakowski M, Zheng X, Jiang F, Rogers T, Szalad A, Chopp M. MiR-146b-5p suppresses EGFR expression and reduces in vitro migration and invasion of glioma. Cancer Invest. 2010; 28:1024-30.
27. Rasheed BK, McLendon RE, Friedman HS, Friedman AH, Fuchs HE, Bigner DD, Bigner SH. Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25. Oncogene. 1995; 10:2243-6.
28. Yin D, Ogawa S, Kawamata N, Leiter A, Ham M, Li D, Doan NB, Said JW, Black KL, Phillip Koeffler H. miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme. Oncogene. 2013; 32:1155-63.
29. Wu X, Bhayani MK, Dodge CT, Nicoloso MS, Chen Y, Yan X, Adachi M, Thomas L, Galer CE, Jiffar T, Pickering CR, Kupferman ME, Myers JN, et al. Coordinated targeting of the EGFR signaling axis by microRNA-27a*. Oncotarget. 2013; 4:1388-98. doi: 10.18632/oncotarget.1239.
30. Wang L, Yao J, Shi X, Hu L, Li Z, Song T, Huang C. MicroRNA-302b suppresses cell proliferation by targeting EGFR in human hepatocellular carcinoma SMMC-7721 cells. BMC Cancer. 2013; 13:448.
31. Denoyelle C, Lambert B, Meryet-Figuière M, Vigneron N, Brotin E, Lecerf C, Abeilard E, Giffard F, Louis MH, Gauduchon P, Juin P, Poulain L. miR-491-5p-induced apoptosis in ovarian carcinoma depends on the direct inhibition of both BCL-XL and EGFR leading to BIM activation. Cell Death Dis. 2014; 5:e1445.
32. Chiyomaru T, Seki N, Inoguchi S, Ishihara T, Mataki H, Matsushita R, Goto Y, Nishikawa R, Tatarano S, Itesako T, Nakagawa M, Enokida H. Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumorsuppressive microRNA-23b/27b cluster in bladder cancer. Int J Oncol. 2015; 46:487-96.
33. Tao J, Wu D, Xu B, Qian W, Li P, Lu Q, Yin C, Zhang W. microRNA-133 inhibits cell proliferation, migration and invasion in prostate cancer cells by targeting the epidermal growth factor receptor. Oncol Rep. juin 2012; 27:1967-75.
34. Cui W, Zhang S, Shan C, Zhou L, Zhou Z. microRNA-133a regulates the cell cycle and proliferation of breast cancer cells by targeting epidermal growth factor receptor through the EGFR/Akt signaling pathway. FEBS J. 2013; 280:3962-74.
35. Xu B, Wang N, Wang X, Tong N, Shao N, Tao J, Li P, Niu X, Feng N, Zhang L, Hua L, Wang Z, Chen M. MiR-146a suppresses tumor growth and progression by targeting EGFR pathway and in a p-ERK-dependent manner in castration-resistant prostate cancer. The Prostate. 2012; 72:1171-8.
36. Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim SO, Du Y, Wang Y, Chang WC, Chen CH, Hsu JL, Wu Y, Lam YC, et al. EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature. 2013; 497:383-7.
37. Chang YS, Chen WY, Yin JJ, Sheppard-Tillman H, Huang J, Liu YN. EGF Receptor Promotes Prostate Cancer Bone Metastasis by Downregulating miR-1 and Activating TWIST1. Cancer Res. 2015; 75:3077-86.
38. Luo H, Zhang H, Zhang Z, Zhang X, Ning B, Guo J, Nie N, Liu B, Wu X. Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res CR. 2009; 28:82.
39. Nagalingam RS, Sundaresan NR, Gupta MP, Geenen DL, Solaro RJ, Gupta M. A cardiac-enriched microRNA, miR-378, blocks cardiac hypertrophy by targeting Ras signaling. J Biol Chem. 2013; 288:11216-32.
40. Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S, Leierseder S, Loyer X, Giacca M, Zentilin L, Thum T, Laggerbauer B, Engelhardt S. MiR-378 controls cardiac hypertrophy by combined repression of mitogenactivated protein kinase pathway factors. Circulation. 2013; 127:2097-106.
41. Avgeris M, Stravodimos K, Scorilas A. Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients. Biol Chem. 2014; 395:1095-104.
42. Wang JL, Hu Y, Kong X, Wang ZH, Chen HY, Xu J, Fang JY. Candidate microRNA biomarkers in human gastric cancer: a systematic review and validation study. PloS One. 2013; 8:e73683.
43. Kikkawa N, Hanazawa T, Fujimura L, Nohata N, Suzuki H, Chazono H, Sakurai D, Horiguchi S, Okamoto Y, Seki N. miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC). Br J Cancer. 2010; 103:877-84.
44. Lv Z, Yang L. MiR-124 inhibits the growth of glioblastoma through the downregulation of SOS1. Mol Med Rep. 2013; 8:345-9.
45. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403:901-6.
46. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Müller P, Spring J, Srinivasan A, Fishman M, et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. 2000; 408:86-9.
47. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell. 2005; 120:635-47.
48. Boyerinas B, Park SM, Hau A, Murmann AE, Peter ME. The role of let-7 in cell differentiation and cancer. Endocr Relat Cancer. 2010; 17:F19-36.
49. Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, Weidhaas JB, Brown D, Bader AG, Slack FJ. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008; 7:759-64.
50. Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, Jacks T. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A. 2008; 105:3903-8.
51. Viswanathan SR, Daley GQ. Lin28: A microRNA regulator with a macro role. Cell. 2010; 140:445-9.
52. 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, 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; 68:8535-40.
53. Christensen BC, Moyer BJ, Avissar M, Ouellet LG, Plaza SL, McClean MD, Marsit CJ, Kelsey KT. A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers. Carcinogenesis. 2009; 30:1003-7.
54. De Ruyck K, Duprez F, Ferdinande L, Mbah C, Rios-Velazquez E, Hoebers F, Praet M, Deron P, Bonte K, Speel EJ, Libbrecht L, De Neve W, Lambin P, et al. A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal cancer. Cancer Epidemiol. 2014; 38:591-8.
55. Kjersem JB, Ikdahl T, Guren T, Skovlund E, Sorbye H, Hamfjord J, Pfeiffer P, Glimelius B, Kersten C, Solvang H, Tveit KM, Kure EH. Let-7 miRNA-binding site polymorphism in the KRAS 3'UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/-cetuximab. BMC Cancer. 2012; 12:534.
56. Smits KM, Paranjape T, Nallur S, Wouters KAD, Weijenberg MP, Schouten LJ, van den Brandt PA, Bosman FT, Weidhaas JB, van Engeland M. A let-7 microRNA SNP in the KRAS 3'UTR is prognostic in early-stage colorectal cancer. Clin Cancer Res. 2011; 17:7723-31.
57. Saridaki Z, Weidhaas JB, Lenz HJ, Laurent-Puig P, Jacobs B, De Schutter J, De Roock W, Salzman DW, Zhang W, Yang D, Pilati C, Bouché O, Piessevaux H, et al. A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy. Clin Cancer Res. 2014; 20:4499-510.
58. Shin KH, Bae SD, Hong HS, Kim RH, Kang MK, Park NH. miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras. Biochem Biophys Res Commun. 2011; 404:896-902.
59. India Project Team of the International Cancer Genome Consortium. Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 2013; 4:2873.
60. Hashimoto Y, Akiyama Y, Otsubo T, Shimada S, Yuasa Y. Involvement of epigenetically silenced microRNA-181c in gastric carcinogenesis. Carcinogenesis. 2010; 31:777-84.
61. Wang XF, Shi ZM, Wang XR, Cao L, Wang YY, Zhang JX, Yin Y, Luo H, Kang CS, Liu N, Jiang T, You Y-P. MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2. J Cancer Res Clin Oncol. 2012; 138:573-84.
62. Zhang Y, Kim J, Mueller AC, Dey B, Yang Y, Lee D., Hachmann J, Finderle S, Park DM, Christensen J, Schiff D, Purow B, Dutta A, Abounader R. Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma. Cell Death Differ. 2014; 21:720-34.
63. Liu Y, Zhang M, Qian J, Bao M, Meng X, Zhang S, Zhang L, Zhao R, Li S, Cao Q, Li P, Ju X, Lu Q, et al. miR-134 functions as a tumor suppressor in cell proliferation and epithelial-to-mesenchymal Transition by targeting KRAS in renal cell carcinoma cells. DNA Cell Biol. 2015; 34:429-36.
64. 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, Castellano L. MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors. PloS One. 2012; 7:e32068.
65. Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, Liu J, Yu J, Chen J. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010; 70:6015-25.
66. Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010; 31:1726-33.
67. Chen X, Guo X, Zhang H, Xiang Y, Chen J, Yin Y, Cai X, Wang K, Wang G, Ba Y, Zhu L, Wang J, Yang R, et al. Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 2009; 28:1385-92.
68. Gao J-S, Zhang Y, Tang X, Tucker LD, Tarwater PM, Quesenberry PJ, Rigoutsos I, Ramratnam B. The Evi1, microRNA-143, K-Ras axis in colon cancer. FEBS Lett. 2011; 585:693-9.
69. Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K. Modulation of microRNA processing by p53. Nature. 2009; 460:529-33.
70. Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD, Maitra A, Mendell JT. Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev. 2010; 24:2754-9.
71. Kopp F, Wagner E, Roidl A. The proto-oncogene KRAS is targeted by miR-200c. Oncotarget. 2014; 5:185-95. doi: 10.18632/oncotarget.1427.
72. Deng M, Tang H, Zhou Y, Zhou M, Xiong W, Zheng Y, Ye Q, Zeng X, Liao Q, Guo X, Li X, Ma J, Li G. miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma. J Cell Sci. 2011; 124:2997-3005.
73. Han Z, Yang Q, Liu B, Wu J, Li Y, Yang C, Jiang Y. MicroRNA-622 functions as a tumor suppressor by targeting K-Ras and enhancing the anticarcinogenic effect of resveratrol. Carcinogenesis. 2012; 33:131-9.
74. Guo LH, Li H, Wang F, Yu J, He JS. The Tumor Suppressor Roles of miR-433 and miR-127 in Gastric Cancer. Int J Mol Sci. 2013; 14:14171-84.
75. Subramani A, Alsidawi S, Jagannathan S, Sumita K, Sasaki AT, Aronow B, Warnick RE, Lawler S, Driscoll JJ. The brain microenvironment negatively regulates miRNA-768-3p to promote K-ras expression and lung cancer metastasis. Sci Rep. 2013; 3:2392.
76. Zhu L, Wang Z, Fan Q, Wang R, Sun Y. microRNA-27a functions as a tumor suppressor in esophageal squamous cell carcinoma by targeting KRAS. Oncol Rep. 2014; 31:280-6.
77. Liao WT, Ye YP, Zhang NJ, Li TT, Wang SY, Cui YM, Qi L, Wu P, Jiao HL, Xie YJ, Zhang C, Wang JX, Ding YQ. MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2. J Pathol. 2014; 232:415-27.
78. Tanic M, Yanowsky K, Rodriguez-Antona C, Andrés R, Márquez-Rodas I, Osorio A, Benitez J, Martinez-Delgado B. Deregulated miRNAs in hereditary breast cancer revealed a role for miR-30c in regulating KRAS oncogene. PloS One. 2012; 7:e38847.
79. Gastaldi C, Bertero T, Xu N, Bourget-Ponzio I, Lebrigand K, Fourre S, Popa A, Cardot-Leccia N, Meneguzzi G, Sonkoly E, Pivarcsi A, Mari B, Barbry P, et al. miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma. Carcinogenesis. 2014; 35:1110-20.
80. Keklikoglou I, Hosaka K, Bender C, Bott A, Koerner C, Mitra D, Will R, Woerner A, Muenstermann E, Wilhelm H, Cao Y, Wiemann S. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Oncogene. 2014; 34:4867-78
81. Frezzetti D, De Menna M, Zoppoli P, Guerra C, Ferraro A, Bello AM, De Luca P, Calabrese C, Fusco A, Ceccarelli M, Zollo M, Barbacid M, Di Lauro R, et al. Upregulation of miR-21 by Ras in vivo and its role in tumor growth. Oncogene. 2011; 30:275-86.
82. Pan X, Wang Z-X, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther. 2010 Dec;10:1224-32.
83. Ren J, Zhu D, Liu M, Sun Y, Tian L. Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma. Eur J Cancer. 2010; 46:3409-16.
84. du Rieu MC, Torrisani J, Selves J, Al Saati T, Souque A, Dufresne M, Tsongalis GJ, Suriawinata AA, Carrère N, Buscail L, Cordelier P. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin Chem. 2010; 56:603-12.
85. Hatley ME, Patrick DM, Garcia MR, Richardson JA, Bassel-Duby R, van Rooij E, Olson EN. Modulation of K-Ras-dependent lung tumorigenesis by MicroRNA-21. Cancer Cell. 2010; 18:282-93.
86. Wang P, Zhu CF, Ma M-Z, Chen G, Song M, Zeng ZL, Lu WH, Yang J, Wen S, Chiao PJ, Hu Y, Huang P. Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer. Oncotarget. 2015; 6:21148-58. doi: 10.18632/oncotarget.4125.
87. Cimino D, De Pittà C, Orso F, Zampini M, Casara S, Penna E, Quaglino E, Forni M, Damasco C, Pinatel E, Ponzone R, Romualdi C, Brisken C, et al. miR148b is a major coordinator of breast cancer progression in a relapseassociated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013; 27:1223-35.
88. Lang MF, Yang S, Zhao C, Sun G, Murai K, Wu X, Wang J, Gao H, Brown CE, Liu X, Zhou J, Peng L, Rossi JJ, Shi Y. Genome-wide profiling identified a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. PloS One. 2012; 7:e36248.
89. Schwartzentruber J, Korshunov A, Liu XY, Jones DTW, Pfaff E, Jacob K, Sturm D, Fontebasso AM, Quang DAK, Tönjes M, Hovestadt V, Albrecht S, Kool M, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012; 482:226-31.
90. Wang L, Shi ZM, Jiang CF, Liu X, Chen QD, Qian X, Li DM, Ge X, Wang X-F, Liu LZ, You Y-P, Liu N, Jiang BH. MiR-143 acts as a tumor suppressor by targeting N-RAS and enhances temozolomide-induced apoptosis in glioma. Oncotarget. 2014; 5:5416-27. doi: 10.18632/oncotarget.2116.
91. Forloni M, Dogra SK, Dong Y, Conte D, Ou J, Zhu LJ, Deng A, Mahalingam M, Green MR, Wajapeyee N. miR-146a promotes the initiation and progression of melanoma by activating Notch signaling. eLife. 2014; 3:e01460.
92. Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen NQN, Scherr M, Castermans K, Malvaux L, Lambert V, Thiry M, Sliwa K, Noel A, Martial JA, et al. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest. 2013 May;123:2143-54.
93. Boll K, Reiche K, Kasack K, Mörbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, Hackermüller J. MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene. 2013; 32:277-85.
94. Chai S, Cambronne XA, Eichhorn SW, Goodman RH. MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9. Proc Natl Acad Sci U S A. 2013; 110:17898-903.
95. Cahill S, Smyth P, Denning K, Flavin R, Li J, Potratz A, Guenther SM, Henfrey R, O'Leary JJ, Sheils O. Effect of BRAFV600E mutation on transcription and posttranscriptional regulation in a papillary thyroid carcinoma model. Mol Cancer. 2007; 6:21.
96. Couts KL, Anderson EM, Gross MM, Sullivan K, Ahn NG. Oncogenic B-Raf signaling in melanoma cells controls a network of microRNAs with combinatorial functions. Oncogene. 2013; 32:1959-70.
97. Chou CK, Chen RF, Chou FF, Chang HW, Chen YJ, Lee YF, Yang KD, Cheng JT, Huang CC, Liu RT. miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation. Thyroid. 2010; 20:489-94.
98. Caramuta S, Egyházi S, Rodolfo M, Witten D, Hansson J, Larsson C, Lui W-O. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol. 2010; 130:2062-70.
99. Nosho K, Igarashi H, Nojima M, Ito M, Maruyama R, Yoshii S, Naito T, Sukawa Y, Mikami M, Sumioka W, Yamamoto E, Kurokawa S, Adachi Y, et al. Association of microRNA-31 with BRAF mutation, colorectal cancer survival and serrated pathway. Carcinogenesis. 2014; 35:776-83.
100. Liu SM, Lu J, Lee HC, Chung FH, Ma N. miR-524-5p suppresses the growth of oncogenic BRAF melanoma by targeting BRAF and ERK2. Oncotarget. 2014; 5:9444-59. doi: 10.18632/oncotarget.2452.
101. Lal A, Thomas MP, Altschuler G, Navarro F, O'Day E, Li XL, Concepcion C, Han YC, Thiery J, Rajani DK, Deutsch A, Hofmann O, Ventura A, et al. Capture of microRNAbound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling. PLoS Genet. 2011; 7:e1002363.
102. Li XJ, Ren ZJ, Tang JH. MicroRNA-34a: a potential therapeutic target in human cancer. Cell Death Dis. 2014; 5:e1327.
103. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem. 2009; 284:5731-41.
104. Zheng D, Radziszewska A, Woo P. MicroRNA 497 modulates interleukin 1 signalling via the MAPK/ERK pathway. FEBS Lett. 2012; 586:4165-72.
105. Nakashima T, Jinnin M, Etoh T, Fukushima S, Masuguchi S, Maruo K, Inoue Y, Ishihara T, Ihn H. Down-regulation of mir-424 contributes to the abnormal angiogenesis via MEK1 and cyclin E1 in senile hemangioma: its implications to therapy. PloS One. 2010; 5:e14334.
106. Hirata H, Hinoda Y, Ueno K, Shahryari V, Tabatabai ZL, Dahiya R. MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer. Carcinogenesis. 2012; 33:41-8.
107. Wang J, Sai K, Chen F, Chen Z. miR-181b modulates glioma cell sensitivity to temozolomide by targeting MEK1. Cancer Chemother Pharmacol. 2013; 72:147-58.
108. Liu J, Xu D, Wang Q, Zheng D, Jiang X, Xu L. LPS induced miR-181a promotes pancreatic cancer cell migration via targeting PTEN and MAP2K4. Dig Dis Sci. 2014; 59:1452-60.
109. Wang L, Shi M, Hou S, Ding B, Liu L, Ji X, Zhang J, Deng Y. MiR-483-5p suppresses the proliferation of glioma cells via directly targeting ERK1. FEBS Lett. 2012; 586:1312-7.
110. Yamane K, Jinnin M, Etoh T, Kobayashi Y, Shimozono N, Fukushima S, Masuguchi S, Maruo K, Inoue Y, Ishihara T, Aoi J, Oike Y, Ihn H. Down-regulation of miR-124/-214 in cutaneous squamous cell carcinoma mediates abnormal cell proliferation via the induction of ERK. J Mol Med. 2013; 91:69-81.
111. Stowe IB, Mercado EL, Stowe TR, Bell EL, Oses-Prieto JA, Hernández H, Burlingame AL, McCormick F. A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. Genes Dev. 2012; 26:1421-6.
112. Sharma SB, Lin CC, Farrugia MK, McLaughlin SL, Ellis EJ, Brundage KM, Salkeni MA, Ruppert JM. MicroRNAs 206 and 21 cooperate to promote RAS-extracellular signalregulated kinase signaling by suppressing the translation of RASA1 and SPRED1. Mol Cell Biol. 15 nov 2014; 34:4143-64.
113. Anand S, Majeti BK, Acevedo LM, Murphy EA, Mukthavaram R, Scheppke L, Huang M, Shields DJ, Lindquist JN, Lapinski PE, King PD, Weis SM, Cheresh DA. MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Nat Med. 2010; 16:909-14.
114. Sun D, Yu F, Ma Y, Zhao R, Chen X, Zhu J, Zhang CY, Chen J, Zhang J. MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1). J Biol Chem. 2013; 288:9508-18.
115. Masliah-Planchon J, Pasmant E, Luscan A, Laurendeau I, Ortonne N, Hivelin M, Varin J, Valeyrie-Allanore L, Dumaine V, Lantieri L, Leroy K, Parfait B, Wolkenstein P, et al. MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis. BMC Genomics. 2013; 14:473.
116. Chai G, Liu N, Ma J, Li H, Oblinger JL, Prahalad AK, Gong M, Chang LS, Wallace M, Muir D, Guha A, Phipps RJ, Hock JM, Yu X. MicroRNA-10b regulates tumorigenesis in neurofibromatosis type 1. Cancer Sci. 2010; 101:1997-2004.
117. Mavrakis KJ, Van Der Meulen J, Wolfe AL, Liu X, Mets E, Taghon T, Khan AA, Setty M, Setti M, Rondou P, Vandenberghe P, Delabesse E, Benoit Y, et al. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat Genet. 2011; 43:673-8.
118. García-Ortí L, Cristóbal I, Cirauqui C, Guruceaga E, Marcotegui N, Calasanz MJ, Castello-Cros R, Odero MD. Integration of SNP and mRNA arrays with microRNA profiling reveals that MiR-370 is upregulated and targets NF1 in acute myeloid leukemia. PloS One. 2012; 7:e47717.
119. Boudry-Labis E, Roche-Lestienne C, Nibourel O, Boissel N, Terre C, Perot C, Eclache V, Gachard N, Tigaud I, Plessis G, Cuccuini W, Geffroy S, Villenet C, et al. Neurofibromatosis-1 gene deletions and mutations in de novo adult acute myeloid leukemia. Am J Hematol. 2013; 88:306-11.
120. Tan X, Wang S, Yang B, Zhu L, Yin B, Chao T, Zhao J, Yuan J, Qiang B, Peng X. The CREB-miR-9 negative feedback minicircuitry coordinates the migration and proliferation of glioma cells. PloS One. 2012; 7:e49570.
121. Lenarduzzi M, Hui ABY, Alajez NM, Shi W, Williams J, Yue S, O'Sullivan B, Liu F-F. MicroRNA-193b enhances tumor progression via down regulation of neurofibromin 1. PloS One. 2013; 8:e53765.
122. Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 2006; 6:259-69.
123. Pichler M, Calin GA. MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients. Br J Cancer. 2015; 113:569-73.
124. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids-the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011; 8:467-77.
125. Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011; 11:849-64.
126. Zhang W, Winder T, Ning Y, Pohl A, Yang D, Kahn M, Lurje G, Labonte MJ, Wilson PM, Gordon MA, Hu-Lieskovan S, Mauro DJ, Langer C, et al. A let-7 microRNAbinding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy. Ann Oncol. 2011; 22:104-9.
127. Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014; 13:622-38.
128. Kasinski AL, Slack FJ. miRNA-34 prevents cancer initiation and progression in a therapeutically resistant K-ras and p53-induced mouse model of lung adenocarcinoma. Cancer Res. 2012; 72:5576-87.