Micrornas in cancer: A historical perspective on the path from discovery to therapy

Cancers

Volumn 7, Issue 3, 2015, Pages 1388-1405

  Orellana, Esteban A ^a,b   Kasinski, Andrea L ^a  

^a PURDUE UNIVERSITY   (United States)

^b PURDUE UNIVERSITY   (United States)

Author keywords

Cancer; History; microRNA; Therapeutics

Indexed keywords

MICRORNA; MICRORNA 155; MICRORNA 15A; MICRORNA 16 1; MICRORNA 21; MICRORNA 27B; MICRORNA 29A; MICRORNA 34A; MICRORNA 34B; MICRORNA 34C; MICRORNA LET 7; MIRAVIRSEN; PARVOVIRUS VECTOR; PROTEIN P53; UNCLASSIFIED DRUG;

3' UNTRANSLATED REGION; 5' UNTRANSLATED REGION; BIOGENESIS; CAENORHABDITIS ELEGANS; CANCER DIAGNOSIS; CANCER GENE THERAPY; CANCER PROGNOSIS; CANCER SURVIVAL; CARCINOGENESIS; CELL FATE; CHRONIC HEPATITIS C; CHRONIC LYMPHATIC LEUKEMIA; DRUG EFFICACY; GENE EXPRESSION; GENE FUNCTION; GENE REGULATORY NETWORK; HUMAN; LIPOSOMAL GENE DELIVERY SYSTEM; LIVER CANCER; METASTASIS POTENTIAL; NEOPLASM; NONHUMAN; ONCOGENE C MYC; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); REGULATORY MECHANISM; REVIEW; RNA ANALYSIS; RNA PROCESSING; RNA SEQUENCE; SINGLE NUCLEOTIDE POLYMORPHISM; SURVIVAL PREDICTION; TRANSCRIPTION REGULATION; VIRAL GENE DELIVERY SYSTEM;

EID: 84938536913     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers7030842     Document Type: Review

References (93)

1. Lee, R.; Feinbaum, R.; Ambros, V. A short history of a short RNA. Cell 2004, 116, S89–S92. [CrossRef]
2. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 1974, 77, 71–94. [PubMed]
3. Horvitz, H.R.; Sulston, J.E. Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics 1980, 96, 435–454. [PubMed]
4. Chalfie, M.; Horvitz, H.R.; Sulston, J.E. Mutations that lead to reiterations in the cell lineages of C. elegans. Cell 1981, 24, 59–69. [CrossRef]
5. Ambros, V.; Horvitz, H.R. Heterochronic mutants of the nematode Caenorhabditis elegans. Science 1984, 226, 409–416. [CrossRef] [PubMed]
6. Ferguson, E.L.; Sternberg, P.W.; Horvitz, H.R. A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. Nature 1987, 326, 259–267. [CrossRef] [PubMed]
7. Lee, R.C.; Feinbaum, R.L.; Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993, 75, 843–854. [CrossRef]
8. Wightman, B.; Ha, I.; Ruvkun, G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993, 75, 855–862. [CrossRef]
9. Reinhart, B.J.; Slack, F.J.; Basson, M.; Pasquinelli, A.E.; Bettinger, J.C.; Rougvie, A.E.; Horvitz, H.R.; Ruvkun, G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000, 403, 901–906. [PubMed]
10. Slack, F.J.; Basson, M.; Liu, Z.; Ambros, V.; Horvitz, H.R.; Ruvkun, G. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol. Cell 2000, 5, 659–669. [CrossRef]
11. Pasquinelli, A.E.; Reinhart, B.J.; Slack, F.; Martindale, M.Q.; Kuroda, M.I.; Maller, B.; Hayward, D.C.; Ball, E.E.; Degnan, B.; Müller, P.; et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000, 408, 86–89. [PubMed]
12. Lee, R.C.; Ambros, V. An extensive class of small RNAs in Caenorhabditis elegans. Science 2001, 294, 862–964. [CrossRef] [PubMed]
13. Lau, N.C.; Lim, L.P.; Weinstein, E.G.; Bartel, D.P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 2001, 294, 858–862. [CrossRef] [PubMed]
14. Lagos-Quintana, M.; Rauhut, R.; Lendeckel, W.; Tuschl, T. Identification of novel genes coding for small expressed RNAs. Science 2001, 294, 853–858. [CrossRef] [PubMed]
15. Reinhart, B.J.; Weinstein, E.G.; Rhoades, M.W.; Bartel, B.; Bartel, D.P. MicroRNAs in plants. Genes Dev. 2002, 16, 1616–1626. [CrossRef] [PubMed]
16. Grishok, A.; Pasquinelli, A.E.; Conte, D.; Li, N.; Parrish, S.; Ha, I.; Baillie, D.L.; Fire, A.; Ruvkun, G.; Mello, C.C. Genes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing. Cell 2001, 106, 23–34. [CrossRef]
17. Hutvágner, G.; McLachlan, J.; Pasquinelli, A.E.; Bálint, E.; Tuschl, T.; Zamore, P.D. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001, 293, 834–838. [CrossRef] [PubMed]
18. Cai, X.; Hagedorn, C.H.; Cullen, B.R. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004, 10, 1957–1966. [CrossRef] [PubMed]
19. Lee, Y. MicroRNA maturation: Stepwise processing and subcellular localization. EMBO J. 2002, 21, 4663–4670. [CrossRef] [PubMed]
20. Lee, Y.; Ahn, C.; Han, J.; Choi, H.; Kim, J.; Yim, J.; Lee, J.; Provost, P.; Rådmark, O.; Kim, S.; Kim, V.N. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003, 425, 415–419. [CrossRef] [PubMed]
21. Lund, E.; Güttinger, S.; Calado, A.; Dahlberg, J.E.; Kutay, U. Nuclear export of microRNA precursors. Science 2004, 303, 95–98. [CrossRef] [PubMed]
22. Zamore, P.D.; Tuschl, T.; Sharp, P.A.; Bartel, D.P. RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101, 25–33. [CrossRef]
23. Hammond, S.M.; Bernstein, E.; Beach, D.; Hannon, G.J. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 2000, 404, 293–296. [PubMed]
24. Lewis, B.P.; Shih, I.; Jones-Rhoades, M.W.; Bartel, D.P.; Burge, C.B. Prediction of Mammalian MicroRNA Targets. Cell 2003, 115, 787–798. [CrossRef]
25. Lytle, J.R.; Yario, T.A.; Steitz, J.A. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 51 UTR as in the 31 UTR. Proc. Natl. Acad. Sci. USA 2007, 104, 9667–9672. [CrossRef] [PubMed]
26. Tay, Y.; Zhang, J.; Thomson, A.M.; Lim, B.; Rigoutsos, I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 2008, 455, 1124–1128. [CrossRef] [PubMed]
27. Helwak, A.; Kudla, G.; Dudnakova, T.; Tollervey, D. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 2013, 153, 654–665. [CrossRef] [PubMed]
28. Guo, H.; Ingolia, N.T.; Weissman, J.S.; Bartel, D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010, 466, 835–840. [CrossRef] [PubMed]
29. Fabian, M.R.; Sonenberg, N.; Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 2010, 79, 351–379. [CrossRef] [PubMed]
30. Vasudevan, S.; Tong, Y.; Steitz, J.A. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007, 318, 1931–1934. [CrossRef] [PubMed]
31. Place, R.F.; Li, L.C.; Pookot, D.; Noonan, E.J.; Dahiya, R. MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. USA 2008, 105, 1608–1613. [CrossRef] [PubMed]
32. Eiring, A.M.; Harb, J.G.; Neviani, P.; Garton, C.; Oaks, J.J.; Spizzo, R.; Liu, S.; Schwind, S.; Santhanam, R.; Hickey, C.J.; et al. MiR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 2010, 140, 652–665. [CrossRef] [PubMed]
33. Tay, Y.; Rinn, J.; Pandolfi, P.P. The multilayered complexity of ceRNA crosstalk and competition. Nature 2014, 505, 344–352. [CrossRef] [PubMed]
34. Salmena, L.; Poliseno, L.; Tay, Y.; Kats, L.; Pandolfi, P.P. A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language? Cell 2011, 146, 353–358. [CrossRef] [PubMed]
35. Calin, G.A.; Dumitru, C.D.; Shimizu, M.; Bichi, R.; Zupo, S.; Noch, E.; Aldler, H.; Rattan, S.; Keating, M.; Rai, K.; et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA 2002, 99, 15524–15529. [CrossRef] [PubMed]
36. Calin, G.A.; Sevignani, C.; Dumitru, C.D.; Hyslop, T.; Noch, E.; Yendamuri, S.; Shimizu, M.; Rattan, S.; Bullrich, F.; Negrini, M.; et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA 2004, 101, 2999–3004. [CrossRef] [PubMed]
37. He, L.; Thomson, J.M.; Hemann, M.T.; Hernando-Monge, E.; Mu, D.; Goodson, S.; Powers, S.; Cordon-Cardo, C.; Lowe, S.W.; Hannon, G.J.; et al. A microRNA polycistron as a potential human oncogene. Nature 2005, 435, 828–833. [CrossRef] [PubMed]
38. O’Donnell, K.A.; Wentzel, E.A.; Zeller, K.I.; Dang, C.V.; Mendell, J.T. C-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005, 435, 839–843. [CrossRef] [PubMed]
39. Bommer, G.T.; Gerin, I.; Feng, Y.; Kaczorowski, A.J.; Kuick, R.; Love, R.E.; Zhai, Y.; Giordano, T.J.; Qin, Z.S.; Moore, B.B.; et al. P53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes. Curr. Biol. 2007, 17, 1298–1307. [CrossRef] [PubMed]
40. Chang, T.C.; Wentzel, E.A.; Kent, O.A.; Ramachandran, K.; Mullendore, M.; Lee, K.H.; Feldmann, G.; Yamakuchi, M.; Ferlito, M.; Lowenstein, C.J.; et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 2007, 26, 745–752. [CrossRef] [PubMed]
41. He, L.; He, X.; Lim, L.P.; de Stanchina, E.; Xuan, Z.; Liang, Y.; Xue, W.; Zender, L.; Magnus, J.; Ridzon, D.; et al. A microRNA component of the p53 tumour suppressor network. Nature 2007, 447, 1130–1134. [CrossRef] [PubMed]
42. Raver-Shapira, N.; Marciano, E.; Meiri, E.; Spector, Y.; Rosenfeld, N.; Moskovits, N.; Bentwich, Z.; Oren, M. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell 2007, 26, 731–743. [CrossRef] [PubMed]
43. Tarasov, V.; Jung, P.; Verdoodt, B.; Lodygin, D.; Epanchintsev, A.; Menssen, A.; Meister, G.; Hermeking, H. 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 2007, 6, 1586–1593. [CrossRef] [PubMed]
44. Saito, Y.; Liang, G.; Egger, G.; Friedman, J.M.; Chuang, J.C.; Coetzee, G.A.; Jones, P.A. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 2006, 9, 435–443. [CrossRef] [PubMed]
45. Lodygin, D.; Tarasov, V.; Epanchintsev, A.; Berking, C.; Knyazeva, T.; Körner, H.; Knyazev, P.; Diebold, J.; Hermeking, H. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 2008, 7, 2591–2600. [CrossRef] [PubMed]
46. Croce, C.M. Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet. 2009, 10, 704–714. [CrossRef] [PubMed]
47. Hata, A.; Lieberman, J. Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci. Signal. 2015, 8, re3. [CrossRef] [PubMed]
48. Brennecke, J.; Hipfner, D.R.; Stark, A.; Russell, R.B.; Cohen, S.M. bantam Encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 2003, 113, 25–36. [CrossRef]
49. Johnson, S.M.; Grosshans, H.; Shingara, J.; Byrom, M.; Jarvis, R.; Cheng, A.; Labourier, E.; Reinert, K.L.; Brown, D.; Slack, F.J. RAS Is Regulated by the let-7 MicroRNA Family. Cell 2005, 120, 635–647. [CrossRef] [PubMed]
50. Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; et al. MiR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA 2005, 102, 13944–13949. [CrossRef] [PubMed]
51. Ma, L.; Teruya-Feldstein, J.; Weinberg, R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007, 449, 682–688. [CrossRef] [PubMed]
52. Tavazoie, S.F.; Alarcón, C.; Oskarsson, T.; Padua, D.; Wang, Q.; Bos, P.D.; Gerald, W.L.; Massagué, J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008, 451, 147–152. [CrossRef] [PubMed]
53. Costinean, S.; Sandhu, S.K.; Pedersen, I.M.; Tili, E.; Trotta, R.; Perrotti, D.; Ciarlariello, D.; Neviani, P.; Harb, J.; Kauffman, L.R.; et al. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice. Blood 2009, 114, 1374–1382. [CrossRef] [PubMed]
54. Medina, P.P.; Nolde, M.; Slack, F.J. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 2010, 467, 86–90. [CrossRef] [PubMed]
55. Mitchell, P.S.; Parkin, R.K.; Kroh, E.M.; Fritz, B.R.; Wyman, S.K.; Pogosova-Agadjanyan, E.L.; Peterson, A.; Noteboom, J.; O’Briant, K.C.; Allen, A.; et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. USA 2008, 105, 10513–10518. [CrossRef] [PubMed]
56. Chim, S.S.C.; Shing, T.K.F.; Hung, E.C.W.; Leung, T.Y.; Lau, T.K.; Chiu, R.W.K.; Lo, Y.M.D. Detection and characterization of placental microRNAs in maternal plasma. Clin. Chem. 2008, 54, 482–490. [CrossRef] [PubMed]
57. Lawrie, C.H.; Gal, S.; Dunlop, H.M.; Pushkaran, B.; Liggins, A.P.; Pulford, K.; Banham, A.H.; Pezzella, F.; Boultwood, J.; Wainscoat, J.S.; et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br. J. Haematol. 2008, 141, 672–675. [CrossRef] [PubMed]
58. Chen, X.; Ba, Y.; Ma, L.; Cai, X.; Yin, Y.; Wang, K.; Guo, J.; Zhang, Y.; Chen, J.; Guo, X.; et al. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008, 18, 997–1006. [CrossRef] [PubMed]
59. Arroyo, J.D.; Chevillet, J.R.; Kroh, E.M.; Ruf, I.K.; Pritchard, C.C.; Gibson, D.F.; Mitchell, P.S.; Bennett, C.F.; Pogosova-Agadjanyan, E.L.; Stirewalt, D.L.; et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. USA 2011, 108, 5003–5008. [CrossRef] [PubMed]
60. Fabbri, M.; Paone, A.; Calore, F.; Galli, R.; Gaudio, E.; Santhanam, R.; Lovat, F.; Fadda, P.; Mao, C.; Nuovo, G.J.; et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc. Natl. Acad. Sci. USA 2012, 109, E2110–E2116. [CrossRef] [PubMed]
61. Melo, S.A.; Sugimoto, H.; O’Connell, J.T.; Kato, N.; Villanueva, A.; Vidal, A.; Qiu, L.; Vitkin, E.; Perelman, L.T.; Melo, C.A.; et al. Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis. Cancer Cell 2014, 26, 707–721. [CrossRef] [PubMed]
62. Takamizawa, J.; Konishi, H.; Yanagisawa, K.; Tomida, S.; Osada, H.; Endoh, H.; Harano, T.; Yatabe, Y.; Nagino, M.; Nimura, Y.; et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004, 64, 3753–3756. [CrossRef] [PubMed]
63. Calin, G.A.; Ferracin, M.; Cimmino, A.; Di Leva, G.; Shimizu, M.; Wojcik, S.E.; Iorio, M.V.; Visone, R.; Sever, N.I.; Fabbri, M.; et al. MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N. Engl. J. Med. 2005, 353, 1793–1801. [CrossRef] [PubMed]
64. Lu, J.; Getz, G.; Miska, E.A.; Alvarez-Saavedra, E.; Lamb, J.; Peck, D.; Sweet-Cordero, A.; Ebert, B.L.; Mak, R.H.; Ferrando, A.A.; et al. MicroRNA expression profiles classify human cancers. Nature 2005, 435, 834–838. [CrossRef] [PubMed]
65. Hamilton, M.P.; Rajapakshe, K.; Hartig, S.M.; Reva, B.; McLellan, M.D.; Kandoth, C.; Ding, L.; Zack, T.I.; Gunaratne, P.H.; Wheeler, D.A.; et al. Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif. Nat. Commun. 2013, [CrossRef] [PubMed]
66. Gahan, P.B. Circulating nucleic acids in plasma and serum: Applications in diagnostic techniques for noninvasive prenatal diagnosis. Int. J.Womens. Health 2013, 5, 177–186. [CrossRef] [PubMed]
67. Boeri, M.; Verri, C.; Conte, D.; Roz, L.; Modena, P.; Facchinetti, F.; Calabrò, E.; Croce, C.M.; Pastorino, U.; Sozzi, G. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc. Natl. Acad. Sci. USA 2011, 108, 3713–3718. [CrossRef] [PubMed]
68. Chin, L.J.; Ratner, E.; Leng, S.; Zhai, R.; Nallur, S.; Babar, I.; Muller, R.U.; Straka, E.; Su, L.; Burki, E.A.; et al. A SNP in a let-7 microRNA complementary site in the KRAS 31 untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008, 68, 8535–8840. [CrossRef] [PubMed]
69. Saridaki, Z.; Weidhaas, J.B.; Lenz, H.J.; Laurent-Puig, P.; Jacobs, B.; De Schutter, J.; De Roock, W.; Salzman, D.W.; Zhang, W.; Yang, D.; 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, 4499–4510. [CrossRef] [PubMed]
70. Sha, D.; Lee, A.M.; Shi, Q.; Alberts, S.R.; Sargent, D.J.; Sinicrope, F.A.; Diasio, R.B. Association study of the let-7 miRNA-complementary site variant in the 31 untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial). Clin. Cancer Res. 2014, 20, 3319–3327. [CrossRef] [PubMed]
71. Chung, C.H.; Lee, J.W.; Slebos, R.J.; Howard, J.D.; Perez, J.; Kang, H.; Fertig, E.J.; Considine, M.; Gilbert, J.; Murphy, B.A.; et al. A 31-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann. Oncol. 2014, 25, 2230–2236. [CrossRef] [PubMed]
72. Bueno Santiago, M.; de Lima Marson, F.A.; Secolin, R.; Ribeiro, J.D.; Passos Lima, C.S.; Bertuzzo, C.S. SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with squamous cell carcinoma of the head and neck. Oncol. Lett. 2014, 7, 1803–1811. [CrossRef] [PubMed]
73. Lee, L.J.; Ratner, E.; Uduman, M.; Winter, K.; Boeke, M.; Greven, K.M.; King, S.; Burke, T.W.; Underhill, K.; Kim, H.; et al. The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. PLoS ONE 2014, 9, e94167. [CrossRef] [PubMed]
74. Pilarski, R.; Patel, D.A.; Weitzel, J.; McVeigh, T.; Dorairaj, J.J.; Heneghan, H.M.; Miller, N.; Weidhaas, J.B.; Kerin, M.J.; McKenna, M.; et al. The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer. PLoS ONE 2012, 7, e37891. [CrossRef] [PubMed]
75. Cerne, J.Z.; Stegel, V.; Gersak, K.; Novakovic, S. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: A case control study. BMC Cancer 2012, [CrossRef] [PubMed]
76. Hutvágner, G.; Simard, M.J.; Mello, C.C.; Zamore, P.D. Sequence-specific inhibition of small RNA function. PLoS Biol. 2004, 2, e98. [CrossRef] [PubMed]
77. Krützfeldt, J.; Rajewsky, N.; Braich, R.; Rajeev, K.G.; Tuschl, T.; Manoharan, M.; Stoffel, M. Silencing of microRNAs in vivo with “antagomirs”. Nature 2005, 438, 685–689. [CrossRef] [PubMed]
78. Elmén, J.; Lindow, M.; Schütz, S.; Lawrence, M.; Petri, A.; Obad, S.; Lindholm, M.; Hedtjärn, M.; Hansen, H.F.; Berger, U.; et al. LNA-mediated microRNA silencing in non-human primates. Nature 2008, 452, 896–899. [CrossRef] [PubMed]
79. Gebert, L.F.R.; Rebhan, M.A.E.; Crivelli, S.E.M.; Denzler, R.; Stoffel, M.; Hall, J. Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res. 2014, 42, 609–621. [CrossRef] [PubMed]
80. Ma, L.; Reinhardt, F.; Pan, E.; Soutschek, J.; Bhat, B.; Marcusson, E.G.; Teruya-Feldstein, J.; Bell, G.W.; Weinberg, R.A. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 2010, 28, 341–347. [CrossRef] [PubMed]
81. Cheng, C.J.; Bahal, R.; Babar, I.A.; Pincus, Z.; Barrera, F.; Liu, C.; Svoronos, A.; Braddock, D.T.; Glazer, P.M.; Engelman, D.M.; et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 2014, 518, 107–110. [CrossRef] [PubMed]
82. Doench, J.G.; Petersen, C.P.; Sharp, P.A. SiRNAs can function as miRNAs. Genes Dev. 2003, 17, 438–442. [CrossRef] [PubMed]
83. Esquela-Kerscher, A.; Trang, P.; Wiggins, J.F.; Patrawala, L.; Cheng, A.; Ford, L.; Weidhaas, J.B.; Brown, D.; Bader, A.G.; Slack, F.J. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 2008, 7, 759–764. [CrossRef] [PubMed]
84. Kota, J.; Chivukula, R.R.; O’Donnell, K.A.; Wentzel, E.A.; Montgomery, C.L.; Hwang, H.W.; Chang, T.C.; Vivekanandan, P.; Torbenson, M.; Clark, K.R.; et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009, 137, 1005–1017. [CrossRef] [PubMed]
85. Wiggins, J.F.; Ruffino, L.; Kelnar, K.; Omotola, M.; Patrawala, L.; Brown, D.; Bader, A.G. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010, 70, 5923–5930. [CrossRef] [PubMed]
86. Trang, P.; Wiggins, J.F.; Daige, C.L.; Cho, C.; Omotola, M.; Brown, D.; Weidhaas, J.B.; Bader, A.G.; Slack, F.J. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol. Ther. 2011, 19, 1116–1122. [CrossRef] [PubMed]
87. Kasinski, A.L.; Slack, F.J. 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, 5576–5587. [CrossRef] [PubMed]
88. Bouchie, A. First microRNA mimic enters clinic. Nat. Biotechnol. 2013, 31, 577. [CrossRef] [PubMed]
89. Beg, M.S.; Borad, M.; Sachdev, J.; Hong, D.S.; Smith, S.; Bader, A.; Stoudemire, J.; Kim, S.; Brenner, A. Abstract CT327: Multicenter phase I study of MRX34, a first-in-class microRNA miR-34 mimic liposomal injection. Cancer Res. 2014, [CrossRef]
90. Kasinski, A.L.; Kelnar, K.; Stahlhut, C.; Orellana, E.; Zhao, J.; Shimer, E.; Dysart, S.; Chen, X.; Bader, A.G.; Slack, F.J. A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer. Oncogene 2015, 34, 3547–3555. [CrossRef] [PubMed]
91. Xue, W.; Dahlman, J.E.; Tammela, T.; Khan, O.F.; Sood, S.; Dave, A.; Cai, W.; Chirino, L.M.; Yang, G.R.; Bronson, R.; et al. Small RNA combination therapy for lung cancer. Proc. Natl. Acad. Sci. USA 2014, 111, E3553–E3561. [CrossRef] [PubMed]
92. Stahlhut, C.; Slack, F.J. Combinatorial action of MicroRNAs let-7 and miR-34 effectively synergizes with erlotinib to suppress non-small cell lung cancer cell proliferation. Cell Cycle 2015, 14, 2171–2180. [CrossRef] [PubMed]
93. Pan, D. Next generation gene delivery approaches: Recent progress and hurdles. Mol. Pharm. 2015, 12, 299–300. [CrossRef] [PubMed]