Managing pancreatic adenocarcinoma: A special focus in microRNA gene therapy

International Journal of Molecular Sciences

Volumn 17, Issue 5, 2016, Pages

  Passadouro, Marta ^a,b   Faneca, Henrique ^a  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Gene therapy; MicroRNA based therapeutics; MicroRNAs; Pancreatic cancer; Pancreatic ductal adenocarcinoma

Indexed keywords

APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CASPASE 9; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; GELATINASE A; GELATINASE B; GEMCITABINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; I KAPPA B; IRINOTECAN; METALLOPROTEINASE; MICRORNA; MICRORNA 100; MICRORNA 148A; MICRORNA 155; MICRORNA 196A; MICRORNA 21; MICRORNA 221; MICRORNA 222; MICRORNA 23A; MOLECULAR MARKER; OXALIPLATIN; PACLITAXEL; PROTEIN P53; SMAD2 PROTEIN; SMALL UNTRANSLATED RNA; STAT3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

APOPTOSIS; CANCER CHEMOTHERAPY; CANCER GENE THERAPY; CANCER INHIBITION; CANCER PROGNOSIS; CANCER THERAPY; CARCINOGENESIS; CELL CYCLE ARREST; CELL INVASION; CELL MIGRATION; CELL MOTILITY; CHEMICAL MODIFICATION; CLINICAL TRIAL (TOPIC); DEREGULATION; EPITHELIAL MESENCHYMAL TRANSITION; HIGH THROUGHPUT SCREENING; MEDIAN SURVIVAL TIME; MICROARRAY ANALYSIS; MORPHOGENESIS; MORTALITY RATE; PANCREAS ADENOCARCINOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; REVIEW; SURVIVAL RATE; TREATMENT RESPONSE; TUMOR GROWTH; TUMOR SUPPRESSOR GENE; UPREGULATION; ADENOCARCINOMA; ANIMAL; GENETICS; HUMAN; METABOLISM; PANCREATIC NEOPLASMS; PROCEDURES; RNAI THERAPEUTICS;

ADENOCARCINOMA; ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; MICRORNAS; PANCREATIC NEOPLASMS; RNAI THERAPEUTICS;

EID: 84966930103     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17050718     Document Type: Review

References (130)

1. Siegel, R.; DeSantis, C.; Virgo, K.; Stein, K.; Mariotto, A.; Smith, T.; Cooper, D.; Gansler, T.; Lerro, C.; Fedewa, S. et al. Cancer treatment and survivorship statistics, 2012. Cancer J. Clin. 2013, 62, 220-241. [CrossRef] [PubMed]
2. Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics, 2012. Cancer J. Clin. 2012, 62, 10-29. [CrossRef] [PubMed]
3. Jemal, A.; Siegel, R.; Ward, E.; Hao, Y.; Xu, J.; Murray, T.; Thun, M.J. Cancer statistics, 2008. Cancer J. Clin. 2008, 58, 71-96. [CrossRef] [PubMed]
4. Hidalgo, M.; von Hoff, D.D. Translational therapeutic opportunities in ductal adenocarcinoma of the pancreas. Clin. Cancer Res. 2012, 18, 4249-4256. [CrossRef] [PubMed]
5. Papadoniou, N.; Kosmas, C.; Gennatas, K.; Polyzos, A.; Mouratidou, D.; Skopelitis, E.; Tzivras, M.; Sougioultzis, S.; Papastratis, G.; Karatzas, G. et al. Prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: A retrospective analysis. Anticancer Res. 2008, 28, 543-549. [PubMed]
6. Saif, M.W. Pancreatic neoplasm in 2011: An update. J. Oncol. Pract. 2011, 12, 316-321.
7. Saif, M.W. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. J. Pancreas 2007, 8, 545-552.
8. Zhu, C.-P.; Shi, J.; Chen, Y.-X.; Xie, W.-F.; Lin, Y. Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis. Radiother. Oncol. 2011, 99, 108-113. [CrossRef] [PubMed]
9. Abrams, R.A.; Lowy, A.M.; O’Reilly, E.M.; Wolff, R.A.; Picozzi, V.J.; Pisters, P.W.T. Combined modality treatment of resectable and borderline resectable pancreas cancer: Expert consensus statement. Ann. Surg. Oncol. 2009, 16, 1751-1756. [CrossRef] [PubMed]
10. Hoffe, S.; Rao, N.; Shridhar, R. Neoadjuvant vs. adjuvant therapy for resectable pancreatic cancer: The evolving role of radiation. Semin. Radiat. Oncol. 2014, 24, 113-125. [CrossRef] [PubMed]
11. Delaney, G.; Jacob, S.; Featherstone, C.; Barton, M. The role of radiotherapy in cancer treatment: Estimating optimal utilization from a review of evidence-based clinical guidelines. Cancer 2005, 104, 1129-1137. [CrossRef] [PubMed]
12. 2+. J. Am. Chem. Soc. 2009, 130, 168-175. [CrossRef] [PubMed]
13. Babaei, M.; Ganjalikhani, M. The potential effectiveness of nanoparticles as radio sensitizers for radiotherapy. Bioimpacts 2014, 4, 15-20. [PubMed]
14. Moertel, C.G.; Reitemeier, R.J.; Donald, S.; Malcolm, Y.; Holbrook, M.A. Combined 5-fluorouracil and supervoltage radiation therapy of lacally unresectable gastrointestinal cancer. Lancelet 1969, 865-867. [CrossRef]
15. Burris, H.A.; Moore, M.J.; Andersen, J.; Green, M.R.; Rothenberg, M.L.; Modiano, M.R.; Cripps, M.C.; Portenoy, R.K.; Storniolo, A.M.; Tarassoff, P. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J. Clin. Oncol. 1997, 15, 2403-2413. [PubMed]
16. Vaccaro, V.; Sperduti, I.; Milella, M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011, 365, 768-769. [PubMed]
17. Von Hoff, D.D.; Ervin, T.; Arena, F.P.; Chiorean, E.G.; Infante, J.; Moore, M.; Seay, T.; Tjulandin, S.A.; Ma W.W.; Saleh, M.N. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 2013, 369, 1691-1703. [CrossRef] [PubMed]
18. Yared, J.A.; Tkaczuk, K.H.R. Update on taxane development: New analogs and new formulations. Drug Des. Dev. Ther. 2012, 6, 371-384.
19. Al-Hajeili, M.; Azmi, A.S.; Choi, M. Nab-paclitaxel: Potential for the treatment of advanced pancreatic cancer. Onco. Targets Ther. 2014, 7, 187-192. [PubMed]
20. Alcindor, T.; Beauger, N. Oxaliplatin: A review in the era of molecularly targeted therapy. Curr. Oncol. 2011, 18, 18-25. [CrossRef] [PubMed]
21. Ychou, M.; Conroy, T.; Seitz, J.F.; Gourgou, S.; Hua, A.; Mery-Mignard, D.; Kramar, A. An open phase I study assessing the feasibility of the triple combination: Oxaliplatin plus irinotecan plus leucovorin/5-fluorouracil every 2 weeks in patients with advanced solid tumors. Ann. Oncol. 2003, 14, 481-489. [CrossRef] [PubMed]
22. 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]
23. Dogini, D.B.; Pascoal, V.D.B.; Avansini, S.H.; Vieira, A.S.; Pereira, T.C.; Lopes-Cendes, I. The new world of RNAs. Genet. Mol. Biol. 2014, 37, 285-293. [CrossRef] [PubMed]
24. Watanabe, Y.; Kanai, A. Systems biology reveals microrna-mediated gene regulation. Front. Genet. 2011, 2, 29. [CrossRef] [PubMed]
25. Eulalio, A.; Huntzinger, E.; Izaurralde, E. Getting to the root of miRNA-mediated gene silencing. Cell 2008, 132, 9-14. [CrossRef] [PubMed]
26. Fromm, B.; Billipp, T.; Peck, L.E.; Johansen, M.; Tarver, J.E.; King, B.L.; Newcomb, J.M.; Sempere, L.F.; Flatmark, K.; Hovig, E. et al. A uniform system for the annotation of vertebrate microRNA genes and the evolution of the human microRNAome. Annu. Rev. Genet. 2015, 49, 213-242. [CrossRef] [PubMed]
27. Zhang, B.; Pan, X.; Cobb, G.P.; Anderson, T. A microRNAs as oncogenes and tumor suppressors. Dev. Biol. 2007, 302, 1-12. [CrossRef] [PubMed]
28. 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]
29. Calin, G.A.; Croce, C.M. MicroRNA signatures in human cancers. Nat. Rev. Cancer 2006, 6, 857-866. [CrossRef] [PubMed]
30. Iorio, M.V.; Ferracin, M.; Liu, C.-G.; Veronese, A.; Spizzo, R.; Sabbioni, S.; Magri, E.; Pedriali, M.; Fabbri, M.; Campiglio, M. et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65, 7065-7070. [CrossRef] [PubMed]
31. Shen, J.; Stass, S.A.; Jiang, F. MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett. 2014, 329, 125-136. [CrossRef] [PubMed]
32. Redova, M.; Sana, J.; Slaby, O. Circulating miRNAs as new blood-based biomarkers for solid cancers. Future Oncol. 2013, 9, 387-402. [CrossRef] [PubMed]
33. Krichevsky, A.M.; Gabriely, G. miR-21: A small multi-faceted RNA. J. Cell. Mol. Med. 2009, 13, 39-53. [CrossRef] [PubMed]
34. Johnson, S.M.; Grosshans, H.; Shingara, J.; Byrom, M.; Jarvis, R.; Cheng, A.; Laborier, 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]
35. Sampson, V.B.; Rong, N.H.; Han, J.; Yang, Q.; Aris, V.; Soteropoulos, P.; Petrelli, N.J.; Dunn, S.P.; Krueger, L.J. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007, 67, 9762-9770. [CrossRef] [PubMed]
36. Johnson, C.D.; Esquela-Kerscher, A.; Stefani, G.; Byrom, M.; Kelnar, K.; Ovcharenko D.; Wilson, M.; Wang, X.; Shelton, J.; Shingara, J. et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007, 67, 7713-7722. [CrossRef] [PubMed]
37. Yu, C.C.; Chen, Y.W.; Chiou, G.Y.; Tsai, L.L.; Huang, P.I.; Chang, C.Y.; Tseng, L.M.; Chiou, S.H.; Yen, S.H.; Chou, M.Y. et al. MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation. Oral Oncol. 2011, 47, 202-210. [CrossRef] [PubMed]
38. Abba, M.; Patil, N.; Allgayer, H. MicroRNAs in the regulation of MMPs and metastasis. Cancers 2014, 6, 625-645. [CrossRef] [PubMed]
39. Kent, O.A.; Mullendore, M.; Wentzel, E.A.; López-Romero, P.; Tan, A.C.; Alvarez, H.; West, K.; Ochs, M.F.; Hidalgo, M.; Arking, D.E. et al. A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biol. Ther. 2009, 8, 2013-2024. [CrossRef] [PubMed]
40. Zhang, Y.; Li, M.; Wang, H.; Fisher, W.E.; Lin, P.H.; Yao, Q.; Chen, C. Profiling of 95 microRNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J. Surg. 2009, 33, 698-709. [CrossRef] [PubMed]
41. Schultz, N.A.; Werner, J.; Willenbrock, H.; Roslind, A.; Giese, N.; Horn, T.; Wøjdemann, M.; Johansen, J.S. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma. Mod. Pathol. 2012, 25, 1609-1622. [CrossRef] [PubMed]
42. Ma, M.-Z.; Kong, X.; Weng, M.-Z.; Cheng, K.; Gong, W.; Quan, Z.-W.; Peng, C.-H. Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: Meta-analysis, experimental validation and clinical significance. J. Exp. Clin. Cancer Res. 2013, 32, 71. [CrossRef] [PubMed]
43. Wang, S.; Zhao, Y.; Li, D.; Zhu, L.; Shen, Z. Identification of biomarkers for the prognosis of pancreatic ductal adenocarcinoma with miRNA microarray data. Int. J. Biol. Markers 2015, 30, e226-e233. [CrossRef] [PubMed]
44. Ouyang, H.; Gore, J.; Deitz, S.; Korc, M. MicroRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30 expression and promoting EGF and TGF-β actions. Oncogene 2014, 33, 4664-4674. [CrossRef] [PubMed]
45. Huang, J.S.; Egger, M.E.; Grizzle W.E.; McNally, L.R. MicroRNA-100 regulates IGF1-receptor expression in metastatic pancreatic cancer cells. Biotech. Histochem. 2013, 88, 397-402. [CrossRef] [PubMed]
46. Gironella, M.; Seux, M.; Xie, M.-J.; Cano, C.; Tomasini, R.; Gommeaux, J.; Garcia, S.; Nowak, J.; Yeung, M.L.; Jeang, K.-T. et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc. Natl. Acad. Sci. USA 2007, 104, 16170-16175. [CrossRef] [PubMed]
47. Huang, C.; Li, H.; Wu, W.; Jiang, T.; Qiu, Z. Regulation of miR-155 affects pancreatic cancer cell invasiveness and migration by modulating the STAT3 signaling pathway through SOCS 1. Oncol. Rep. 2013, 30, 1223-1230. [PubMed]
48. Huang, F.; Tang, J.; Zhuang, X.; Zhuang, Y.; Cheng, W.; Chen, W.; Yao, H.; Zhang, S. miR-196a promotes pancreatic cancer progression by targeting nuclear factor κB-inhibitor α. PLoS ONE 2014, 9, e87897.
49. Liu, M.; Du, Y.; Gao, J.; Liu, J.; Kong, X.; Gong, Y.; Li, Z.; Wu, H.; Chen, H. Aberrant expression miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells. Pancreas 2013, 42, 1169-1181. [CrossRef] [PubMed]
50. Nagao, Y.; Hisaoka, M.; Matsuyama, A.; Kanemitsu, S.; Hamada, T.; Fukuyama, T.; Nakano, R.; Uchiyama, A.; Kawamoto, M.; Yamaguchi, K. et al. Association of MicroRNA-21 Expression with Its Targets, PDCD4 and TIMP3, in Pancreatic Ductal Adenocarcinoma; Nature Publishing Group: London, UK, 2012; Volume 25, pp. 112-121.
51. Wei, X.; Wang W.; Wang, L.; Zhang, Y.; Zhang, X.; Chen, M.; Wang, F.; Yu, J.; Ma, Y.; Sun, G. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4. Cancer Med. 2016, 184, 855-860.
52. Su, A.; He, S.; Tian, B.; Hu, W.; Zhang, Z. MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the epithelial-mesenchymal transition in pancreatic cancer cells. PLoS ONE 2013, 8, e71309. [CrossRef] [PubMed]
53. Passadouro, M.; Pedroso de Lima, M.C.; Faneca, H. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer. Int. J. Nanomed. 2014, 9, 3203-3217.
54. Sarkar, S.; Dubaybo, H.; Ali, S.; Goncalves, P.; Kollepara, S.L.; Sethi, S. Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27kip1, p57kip2, and PUMA. Am. J. Cancer Res. 2013, 3, 465-477. [PubMed]
55. Xu, Q.; Li, P.; Chen, X.; Zong, L.; Jiang, Z.; Nan, L.; Lei, J.; Duan, W.; Zhang, D.; Li, X. et al. miR-221/222 induces pancreatic cancer progression through the regulation of matrix metalloproteinases. Oncotarget 2015, 6, 14153-14164. [CrossRef] [PubMed]
56. Liu, N.; Sun, Y.Y.; Zhang, X.W.; Chen, S.; Wang, Y.; Zhang, Z.X.; Song, S.W.; Qiu, G.B.; Fu W.N. Oncogenic miR-23a in pancreatic ductal adenocarcinogenesis via inhibiting APAF 1. Dig. Dis. Sci. 2015, 60, 2000-2008. [CrossRef] [PubMed]
57. Liffers, S.-T.; Munding, J.B.; Vogt, M.; Kuhlmann, J.D.; Verdoodt, B.; Nambiar, S.; Maghnouj, A.; Mirmohammadsadegh, A.; Hahn, S.A.; Tannapfel, A. MicroRNA-148a is down-regulated in human pancreatic ductal adenocarcinomas and regulates cell survival by targeting CDC25B. Lab. Investig. 2011, 91, 1472-1479. [CrossRef] [PubMed]
58. Zhang, R.; Li, M.; Zang, W.; Chen, X.; Wang, Y.; Li, P.; Du, Y.; Zhao, G.; Li, L. miR-148a regulates the growth and apoptosis in pancreatic cancer by targeting CCKBR and Bcl-2. Tumour Biol. 2014, 35, 837-844. [CrossRef] [PubMed]
59. Zhan, Q.; Fang, Y.; Deng, X.; Chen, H.; Jin, J.; Lu, X.; Peng, C.; Li, H.; Shen, B. The interplay between miR-148a and DNMT1 might be exploited for pancreatic cancer therapy. Cancer Investig. 2015, 33, 267-275. [CrossRef] [PubMed]
60. Zhao, W.G.; Yu, S.N.; Lu, Z.H.; Ma, Y.H.; Gu, Y.M.; Chen, J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis 2010, 31, 1726-1733. [CrossRef] [PubMed]
61. Deng, S.; Zhu, S.; Wang, B.; Li, X.; Liu, Y.; Qin, Q.; Gong, Q.; Niu, Y.; Xiang, C.; Chen, J. et al. Chronic pancreatitis and pancreatic cancer demonstrate active epithelial-mesenchymal transition profile, regulated by miR-217-SIRT1 pathway. Cancer Lett. 2014, 355, 184-191. [CrossRef] [PubMed]
62. Hu, Q.L.; Jiang, Q.Y.; Jin, X.; Shen, J.; Wang, K.; Li, Y.B.; Xu, F.J.; Tang, G.P.; Li, Z.H. Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model. Biomaterials 2013, 34, 2265-2276. [CrossRef] [PubMed]
63. Xia, J.; Duan, Q.; Ahmad, A.; Bao, B.; Banerjee, S.; Shi, Y.; Ma, J.; Geng, J.; Chen, Z.; Rahman, K.M.W. et al. Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells. Curr. Drug Targets 2012, 13, 1750-1756. [CrossRef] [PubMed]
64. Song, S.-D.; Zhou, J.; Zhou, J.; Zhao, H.; Cen, J.-N.; Li, D.-C. MicroRNA-375 targets the 3-phosphoinositide-dependent protein kinase-1 gene in pancreatic carcinoma. Oncol. Lett. 2013, 6, 953-959. [PubMed]
65. Zhou, J.; Song, S.; He, S.; Zhu, X.; Zhang, Y.I.; Yi, B.; Zhang, B.; Qin, G.; Li, D. MicroRNA-375 targets PDK1 in pancreatic carcinoma and suppresses cell growth through the Akt signaling pathway. Int. J. Mol. Med. 2014, 33, 950-956. [PubMed]
66. Klein, E.E.; Longnecker, D.S.; Gutmann, E.J.; Lorenzo, F. MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2012, 17, 5812-5821.
67. Chen, J.; Zheng, B.; Wang, C.; Chen, Y.; Du, C.; Zhao, G.; Zhou, Y.; Shi, Y. Prognostic role of microRNA-100 in various carcinomas: Evidence from six studies. Tumor Biol. 2013, 35, 3067-3071. [CrossRef] [PubMed]
68. Gebeshuber, C.A.; Martinez, J. miR-100 suppresses IGF2 and inhibits breast tumorigenesis by interfering with proliferation and survival signaling. Oncogene 2012, 32, 3306-3310. [CrossRef] [PubMed]
69. LaConti, J.J.; Shivapurkar, N.; Preet, A.; Deslattes Mays, A.; Peran, I.; Kim, S.E.; Marshall, J.L.; Riegel, A.T.; Wellstein, A. Tissue and serum microRNAs in the KrasG12D transgenic animal model and in patients with pancreatic cancer. PLoS ONE 2011, 6, e20687. [CrossRef] [PubMed]
70. Jung, D.E.; Wen, J.; Oh, T.; Song, S.Y. Differentially expressed microRNAs in pancreatic cancer stem cells. Pancreas 2011, 40, 1180-1187. [CrossRef] [PubMed]
71. Ryu, J.K.; Hong, S.M.; Karikari, C.A.; Hruban, R.H.; Goggins, M.G.; Maitra, A. Aberrant microRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatology 2010, 10, 66-73. [CrossRef] [PubMed]
72. Greither, T.; Grochola, L.F.; Udelnow, A.; Lautenschläger, C.; Würl, P.; Taubert, H. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int. J. Cancer 2010, 126, 73-80. [CrossRef] [PubMed]
73. Zhu, S.; Wu, H.; Wu, F.; Nie, D.; Sheng, S.; Mo, Y.-Y. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 2008, 18, 350-359. [CrossRef] [PubMed]
74. Wang, Z.-X.; Lu, B.-B.; Wang, H.; Cheng, Z.-X.; Yin, Y.-M. MicroRNA-21 modulates chemosensitivity of breast cancer cells to doxorubicin by targeting PTEN. Arch. Med. Res. 2011, 42, 281-290. [CrossRef] [PubMed]
75. Meng, F.; Henson, R.; Wehbe-Janek, H.; Ghoshal, K.; Jacob, S.T.; Patel, T. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007, 133, 647-658. [CrossRef] [PubMed]
76. Dillhoff, M.; Liu, J.; Frankel, W.; Croce, C.; Bloomston, M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J. Gastrointest. Surg. 2008, 12, 2171-2176. [CrossRef] [PubMed]
77. Giovannetti, E.; Funel, N.; Peters, G.J.; del Chiaro, M.; Erozenci, L.A.; Vasile, E.; Leon, L.G.; Pollina, L.E.; Groen, A. et al. MicroRNA-21 in pancreatic cancer: Correlation with clinical outcome and pharmacologic aspects underlying its role in the modulation of gemcitabine activity. Cancer Res. 2010, 70, 4528-4538. [CrossRef] [PubMed]
78. Du Rieu, M.C.; Torrisani, J.; Selves, J.; Al Saati, T.; Souque, A.; Dufresne, M.; Tsongalis, G.J.; Suriawinata, A.A.; Carrère, N.; Buscail, L. et al. MicroRNA-21 is induced early in pancreatic ductal adenocarcinoma precursor lesions. Clin. Chem. 2010, 56, 603-612. [CrossRef] [PubMed]
79. Han, M.; Liu, M.; Wang, Y.; Chen, X.; Xu, J.; Sun, Y.; Zhao, L.; Qu, H.; Fan, Y.; Wu, C. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS ONE 2012, 7, e39520. [CrossRef] [PubMed]
80. Mace, T.A.; Collins, A.L.; Wojcik, S.E.; Croce, C.M.; Lesinski, G.B.; Bloomston, M. Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells. J. Surg. Res. 2013, 184, 855-860. [CrossRef] [PubMed]
81. Kadera, B.E.; Li, L.; Toste, P.A.; Wu, N.; Adams, C.; Dawson, D.W.; Donahue, T.R. MicroRNA-21 in pancreatic ductal adenocarcinoma tumor-associated fibroblasts promotes metastasis. PLoS ONE 2013, 8, e71978. [CrossRef] [PubMed]
82. Farrell, J.J.; Toste, P.; Wu, N.; Li, L.; Wong, J.; Malkhassian, D.; Tran, L.M.; Wu, X.; Li, X.; Dawson, D. et al. Endoscopically acquired pancreatic cyst fluid microRNA 21 and 221 are associated with invasive cancer. Am. J. Gastroenterol. 2013, 108, 1352-1359. [CrossRef] [PubMed]
83. An, J.; Pan, Y.; Yan, Z.; Li W.; Cui, J.; Yuan, J.; Tian, L.; Xing, R.; Lu, Y. MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells. J. Cell. Biochem. 2013, 114, 2160-2169. [CrossRef] [PubMed]
84. Liu, X.; Ru, J.; Zhang, J.; Zhu, L.H.; Liu, M.; Li, X.; Tang, H. miR-23a targets interferon regulatory factor 1 and modulates cellular proliferation and paclitaxel-induced apoptosis in gastric adenocarcinoma cells. PLoS ONE 2013, 8, e64707.
85. Zheng, H.; Li, W.; Wang, Y.; Xie, T.; Cai, Y.; Wang, Z.; Jiang, B. miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during FAS-induced EMT in gastrointestinal cancer. Carcinogenesis 2014, 35, 173-183. [CrossRef] [PubMed]
86. Jahid, S.; Sun, J.; Edwards, R.A.; Dizon, D.; Panarelli, N.C.; Milsom, J.W.; Sikandar, S.S.; Gumus, Z.H.; Lipkin, S.M. miR-23a promotes the transition from indolent to invasive colorectal cancer. Cancer Discov. 2012, 2, 540-553. [CrossRef] [PubMed]
87. Wang, Z.; Wei, W.; Sarkar, F.H. miR-23a, a critical regulator of “migR”ation and metastasis in colorectal cancer. Cancer Discov. 2012, 2, 489-491. [CrossRef] [PubMed]
88. Shang, J.; Yang, F.; Wang, Y.; Wang, Y.; Xue, G.; Mei, Q.; Wang, F.; Sun, S. MicroRNA-23a antisense enhances 5-fluorouracil chemosensitivity through APAF-1/caspase-9 apoptotic pathway in colorectal cancer cells. J. Cell. Biochem. 2014, 115, 772-784. [CrossRef] [PubMed]
89. Pellegrino, L.; Stebbing, J.; Braga, V.M.; Frampton, A.E.; Jacob, J.; Buluwela, L.; Jiao, L.R.; Periyasamy, M.; Madsen, C.D.; Caley, M.P. et al. miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts. Nucleic Acids Res. 2013, 41, 5400-5412. [CrossRef] [PubMed]
90. Sakamoto, N.; Naito, Y.; Oue, N.; Sentani, K.; Uraoka, N.; Zarni Oo, H.; Yanagihara, K.; Aoyagi, K.; Sasaki, H.; Yasui, W. MicroRNA-148a is downregulated in gastric cancer, targets MMP7, and indicates tumor invasiveness and poor prognosis. Cancer Sci. 2014, 105, 236-243. [CrossRef] [PubMed]
91. Zhang, Z.; Zheng, W.; Hai, J. MicroRNA-148b expression is decreased in hepatocellular carcinoma and associated with prognosis. Med. Oncol. 2014, 31, 984. [CrossRef] [PubMed]
92. Li, J.; Song, Y.; Wang, Y.; Luo, J.; Yu W. MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol. Cell. Biochem. 2013, 380, 277-282. [CrossRef] [PubMed]
93. Wang, S.H.; Li, X.; Zhou, L.S.; Cao, Z.W.; Shi, C.; Zhou, C.Z.; Wen, Y.G.; Shen, Y.; Li, J.K. MicroRNA-148a suppresses human gastric cancer cell metastasis by reversing epithelial-to-mesenchymal transition. Tumor Biol. 2013, 34, 3705-3712. [CrossRef] [PubMed]
94. Jiang, F.; Mu, J.; Wang, X.; Ye, X.; Si, L.; Ning, S.; Li, Z.; Li, Y. The repressive effect of miR-148a on TGF β-SMADs signal pathway is involved in the glabridin-induced inhibition of the cancer stem cells-like properties in hepatocellular carcinoma cells. PLoS ONE 2014, 9, e96698. [CrossRef] [PubMed]
95. Hanoun, N.; Delpu, Y.; Suriawinata, A.A.; Bournet, B.; Bureau, C.; Selves, J.; Tsongalis, G.J.; Dufresne, M.; Buscail, L.; Cordelier, P. et al. The silencing of microRNA 148a production by DNA hypermethylation is an early event in pancreatic carcinogenesis. Clin. Chem. 2010, 56, 1107-1118. [CrossRef] [PubMed]
96. Delpu, Y.; Lulka, H.; Sicard, F.; Saint-Laurent, N.; Lopez, F.; Hanoun, N.; Buscail, L.; Cordelier, P.; Torrisani, J. The rescue of miR-148a expression in pancreatic cancer: An inappropriate therapeutic tool. PLoS ONE 2013, 8, e55513. [CrossRef] [PubMed]
97. Li, H.; Zhao, J.; Zhang, J.W.; Huang, Q.Y.; Huang, J.Z.; Chi, L.S.; Tang, H.J.; Liu, G.Q.; Zhu, D.J.; Ma W.M. MicroRNA-217, down-regulated in clear cell renal cell carcinoma and associated with lower survival, suppresses cell proliferation and migration. Neoplasma 2013, 60, 511-515. [CrossRef] [PubMed]
98. Su, J.; Wang, Q.; Liu, Y.; Zhong, M. miR-217 inhibits invasion of hepatocellular carcinoma cells through direct suppression of E2F3. Mol. Cell. Biochem. 2014, 392, 289-296. [CrossRef] [PubMed]
99. Nishioka, C.; Ikezoe, T.; Yang, J.; Nobumoto, A.; Tsuda, M.; Yokoyama, A. Downregulation of miR-217 correlates with resistance of Ph+ leukemia cells to ABL tyrosine kinase inhibitors. Cancer Sci. 2014, 105, 297-307. [CrossRef] [PubMed]
100. Nalls, D.; Tang, S.-N.; Rodova, M.; Srivastava, R.K.; Shankar, S. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS ONE 2011, 6, e24099. [CrossRef] [PubMed]
101. Szafranska, A.E.; Davison, T.S.; John, J.; Cannon, T.; Sipos, B.; Maghnouj, A.; Labourier, E.; Hahn, S.A. MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene 2007, 26, 4442-4452. [CrossRef] [PubMed]
102. Hong, S.; Noh, H.; Teng, Y.; Shao, J.; Rehmani, H.; Ding, H.-F.; Dong, Z.; Su, S.-B.; Shi, H.; Kim, J. et al. SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition inducer in breast cancer cells. Neoplasia 2014, 16, 279-290. [CrossRef] [PubMed]
103. Ye, X.-M.; Zhu, H.-Y.; Bai W.-D.; Wang, T.; Wang, L.; Chen, Y.; Yang, A.-G.; Jia, L.-T. Epigenetic silencing of miR-375 induces trastuzumab resistance in HER2-positive breast cancer by targeting IGF1R. BMC Cancer 2014, 14, 134. [CrossRef] [PubMed]
104. Yu, H.; Jiang, L.; Sun, C.; Guo, L.; Lin, M.; Huang, J.; Zhu, L. Decreased circulating miR-375: A potential biomarker for patients with non-small-cell lung cancer. Gene 2013, 534, 60-65. [CrossRef] [PubMed]
105. Yan, J.W.; Lin, J.S.; He, X.X. The emerging role of miR-375 in cancer. Int. J. Cancer 2013, 135, 1011-1018. [CrossRef] [PubMed]
106. Zhou, J.; Song, S.; Cen, J.; Zhu, D.; Li, D.; Zhang, Z. MicroRNA-375 is downregulated in pancreatic cancer and inhibits cell proliferation in vitro. Oncol. Res. 2012, 20, 197-203. [CrossRef] [PubMed]
107. Basu, A.; Alder, H.; Khiyami, A.; Leahy, P.; Croce, C.M.; Haldar, S. MicroRNA-375 and microRNA-221: Potential noncoding RNAs associated with antiproliferative activity of benzyl isothiocyanate in pancreatic cancer. Genes Cancer 2011, 2, 108-119. [CrossRef] [PubMed]
108. Ebert, M.S.; Sharp, P.A. MicroRNA sponges: Progress and possibilities. RNA 2010, 16, 2043-2050. [CrossRef] [PubMed]
109. Schwarz, D.S.; Hutvágner, G.; Du, T.; Xu, Z.; Aronin, N.; Zamore, P.D. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003, 115, 199-208. [CrossRef]
110. Lennox, K.A.; Behlke, M.A. Chemical modification and design of anti-miRNA oligonucleotides. Gene Ther. 2011, 18, 1111-1120. [CrossRef] [PubMed]
111. Kauppinen, S.; Vester, B.; Wengel, J. Locked nucleic acid: High-affinity targeting of complementary RNA for RNomics. Handb. Exp. Pharmacol. 2006, 173, 405-422. [PubMed]
112. Gao, P.; Tchernyshyov, I.; Chang, T.-C.; Lee, Y.-S.; Kita, K.; Ochi, T.; Zeller, K.I.; de Marzo, A.M.; van Eyk, J.E.; Mendell, J.T. et al. c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 2009, 458, 762-765. [CrossRef] [PubMed]
113. 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]
114. Wu, Y.; Crawford, M.; Mao, Y.; Lee, R.J.; Davis, I.C.; Elton, T.S.; Lee, L.J.; Nana-Sinkam, S.P. Therapeutic delivery of microRNA-29b by cationic lipoplexes for lung cancer. Mol. Ther. Nucleic Acids 2013, 2, e84. [CrossRef] [PubMed]
115. Ohno, S.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T. et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 2012, 21, 185-191. [CrossRef] [PubMed]
116. Lou, W.; Chen, Q.; Ma, L.; Liu, J.; Yang, Z.; Shen, J.; Cui, Y.; Bian, X.W.; Qian, C. Oncolytic adenovirus co-expressing miRNA-34a and IL-24 induces superior antitumor activity in experimental tumor model. J. Mol. Med. 2013, 91, 715-725. [CrossRef] [PubMed]
117. Pramanik, D.; Campbell, N.R.; Karikari, C.; Chivukula, R.; Kent, O.A.; Mendell, J.T.; Maitra, A. Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol. Cancer Ther. 2011, 10, 1470-1480. [CrossRef] [PubMed]
118. Jopling, C.L.; Yi, M.; Lancaster, A.M.; Lemon, S.M.; Sarnow, P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005, 309, 1577-1581. [CrossRef] [PubMed]
119. Hydbring, P.; Badalian-Very, G. Clinical applications of microRNAs. F1000Research 2013, 2. [CrossRef]
120. Bader, A.G. miR-34—A microRNA replacement therapy is headed to the clinic. Front. Genet. 2012, 3, 120. [CrossRef] [PubMed]
121. Nana-Sinkam, S.P.; Croce, C.M. Clinical applications for microRNAs in cancer. Clin. Pharmacol. Ther. 2013, 93, 98-104. [CrossRef] [PubMed]
122. 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]
123. Hermeking, H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010, 17, 193-199. [CrossRef] [PubMed]
124. Misso, G.; di Martino, M.T.; de Rosa, G.; Farooqi, A.A.; Lombardi, A.; Campani, V.; Zarone, M.R.; Gullà, A.; Tagliaferri, P.; Tassone, P. et al. miR-34: A new weapon against cancer? Mol. Ther. Nucleic Acids 2014, 3, e194. [CrossRef] [PubMed]
125. Calura, E.; Martini, P.; Sales, G.; Beltrame, L.; Chiorino, G.; D’Incalci, M.; Marchini, S.; Romualdi, C. Wiring miRNAs to pathways: A topological approach to integrate miRNA and mRNA expression profiles. Nucleic Acids Res. 2014, 42. [CrossRef] [PubMed]
126. Creighton, C.J.; Nagaraja, A.K.; Hanash, S.M.; Matzuk, M.M.; Gunaratne, P.H. A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions. RNA 2008, 14, 2290-2296. [CrossRef] [PubMed]
127. Ghosh, Z.; Chakrabarti, J.; Mallick, B. miRNomics—The bioinformatics of microRNA genes. Biochem. Biophys. Res. Commun. 2007, 363, 6-11. [CrossRef] [PubMed]
128. Vlachos, I.S.; Hatzigeorgiou, A.G. Online resources for miRNA analysis. Clin. Biochem. 2013, 46, 879-900. [CrossRef] [PubMed]
129. John, B.; Enright, A.J.; Aravin, A.; Tuschl, T.; Sander, C.; Marks, D.S. Human microRNA targets. PLoS Biol. 2004, 2, e363. [CrossRef] [PubMed]
130. Costa, P.M.; Cardoso, A.L.; Nóbrega, C.; Pereira de Almeida, L.F.; Bruce, J.N.; Canoll, P.; Pedroso de Lima, M.C. MicroRNA-21 silencing enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma. Hum. Mol. Genet. 2013, 22, 904-918. [CrossRef] [PubMed]