title: MicroRNAs and drug resistance in prostate cancers.
abstract: Prostate cancer is the second leading cause of cancer related death in American men. Androgen deprivation therapy (ADT) is used to treat patients with aggressive prostate cancers. After androgen deprivation therapy, prostate cancers slowly progress to an androgen-independent status. Taxanes (e.g., docetaxel) are used as standard treatments for androgen-independent prostate cancers. However, these chemotherapeutic agents will eventually become ineffective due to the development of drug resistance. A microRNA (miRNA) is a small noncoding RNA molecule, which can regulate gene expression at the post-transcription level. miRNAs elicit their effects by binding to the 3'-untranslated region (3'-UTR) of their target mRNAs, leading to the inhibition of translation or the degradation of the mRNAs. miRNAs have received increasing attention as targets for cancer therapy, as they can target multiple signaling pathways related to tumor progression, metastasis, invasion, and chemoresistance. Emerging evidence suggests that aberrant expression of miRNAs can lead to the development of resistant prostate cancers. Here, we discuss the roles of miRNAs in the development of resistant prostate cancers and their involvement in various drug resistant mechanisms including androgen signaling, apoptosis avoidance, multiple drug resistance (MDR) transporters, epithelialmesenchymal transition (EMT), and cancer stem cells (CSCs). In addition, we also discuss strategies for treating resistant prostate cancers by targeting specific miRNAs. Different delivery strategies are also discussed with focus on those that have been successfully used in human clinical trials.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University , Hampton, Virginia 23668, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Ram I
authors.initials: RI
authors.lastname: Mahato
mesh_terms: D020413:3' Untranslated Regions; D000728:Androgens / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000737:chemistry; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008055:Lipids / Q000737:chemistry; D046911:Macromolecular Substances; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D000728:Androgens; D003505:Cyclodextrins; D008055:Lipids; D046911:Macromolecular Substances; D035683:MicroRNAs; D011108:Polymers
references.citation: PLoS One. 2013 Aug 07;8(8):e71130
references.pmid: 23940701
references.citation: Mol Ther. 2010 Jul;18(7):1357-64
references.pmid: 20461061
references.citation: Mol Cell Biochem. 2010 Jul;340(1-2):265-73
references.pmid: 20224986
references.citation: Acta Pharmacol Sin. 2010 Jul;31(7):867-73
references.pmid: 20581857
references.citation: Nat Med. 2011 Feb;17(2):211-5
references.pmid: 21240262
references.citation: Cancer Res. 2011 Jan 15;71(2):583-92
references.pmid: 21224345
references.citation: Biochem Biophys Res Commun. 2008 Dec 5;377(1):114-9
references.pmid: 18834855
references.citation: Adv Drug Deliv Rev. 2011 Jan-Feb;63(1-2):47-68
references.pmid: 21156190
references.citation: Cancer Res. 2008 Aug 1;68(15):6162-70
references.pmid: 18676839
references.citation: Mol Pharm. 2011 Oct 3;8(5):1955-61
references.pmid: 21793576
references.citation: J Natl Cancer Inst. 2010 May 5;102(9):638-49
references.pmid: 20339138
references.citation: BJU Int. 2008 Dec;102(11):1694-9
references.pmid: 18710444
references.citation: Clin Cancer Res. 2013 Jan 1;19(1):73-84
references.pmid: 23147995
references.citation: Oncogene. 2012 Oct 11;31(41):4460-71
references.pmid: 22266859
references.citation: Biochem Pharmacol. 2011 Mar 15;81(6):783-92
references.pmid: 21219875
references.citation: Mol Cancer. 2010 Jan 21;9:12
references.pmid: 20092645
references.citation: Biol Cell. 2012 Jan;104(1):3-12
references.pmid: 22188537
references.citation: Cancer Res. 2013 Feb 1;73(3):1232-44
references.pmid: 23233736
references.citation: Int J Cancer. 2010 Dec 15;127(12):2768-76
references.pmid: 21351256
references.citation: J Urol. 1993 Nov;150(5 Pt 1):1544-7
references.pmid: 8105110
references.citation: Cell. 2002 Jan 25;108(2):153-64
references.pmid: 11832206
references.citation: Mol Ther Nucleic Acids. 2013 Oct 01;2:e126
references.pmid: 24084846
references.citation: J Pharm Sci. 1995 Nov;84(11):1267-71
references.pmid: 8587040
references.citation: Eur Neurol. 2013;69(5):296-303
references.pmid: 23445755
references.citation: Nat Biotechnol. 2013 Jul;31(7):577
references.pmid: 23839128
references.citation: Mol Pharm. 2009 May-Jun;6(3):659-68
references.pmid: 19267452
references.citation: Opt Lett. 2013 Feb 1;38(3):296-8
references.pmid: 23381416
references.citation: Br J Cancer. 2013 Apr 30;108(8):1668-76
references.pmid: 23571738
references.citation: Nat Rev Drug Discov. 2006 Mar;5(3):219-34
references.pmid: 16518375
references.citation: PLoS One. 2012;7(6):e40021
references.pmid: 22768203
references.citation: PLoS One. 2013 Nov 26;8(11):e82062
references.pmid: 24303078
references.citation: PLoS One. 2013 Aug 01;8(8):e70372
references.pmid: 23936419
references.citation: Clin Chem. 2011 Oct;57(10):1366-75
references.pmid: 21956922
references.citation: PLoS One. 2013;8(3):e60034
references.pmid: 23527297
references.citation: Cancer Res. 2009 Apr 15;69(8):3356-63
references.pmid: 19351832
references.citation: Biochem Pharmacol. 2014 Feb 1;87(3):515-22
references.pmid: 24184504
references.citation: Drug Resist Updat. 2008 Aug-Oct;11(4-5):123-51
references.pmid: 18718806
references.citation: Mol Cell Biol. 2008 Sep;28(17):5147-61
references.pmid: 18573883
references.citation: Mol Ther. 2013 Aug;21(8):1570-8
references.pmid: 23799535
references.citation: Int J Oncol. 2013 Jul;43(1):307-14
references.pmid: 23612742
references.citation: Cancer Res. 2009 Jul 15;69(14):5820-8
references.pmid: 19584296
references.citation: RNA. 2010 Nov;16(11):2043-50
references.pmid: 20855538
references.citation: Nature. 2005 Dec 1;438(7068):685-9
references.pmid: 16258535
references.citation: Gene. 2013 Apr 15;518(2):296-302
references.pmid: 23370341
references.citation: Angew Chem Int Ed Engl. 2012 Aug 20;51(34):8529-33
references.pmid: 22782619
references.citation: Prostate. 2011 Apr;71(5):538-49
references.pmid: 20886540
references.citation: J Biomater Sci Polym Ed. 2010;21(3):303-14
references.pmid: 20178687
references.citation: Cancer Res. 2010 Oct 15;70(20):8108-16
references.pmid: 20813833
references.citation: PLoS One. 2012;7(12):e52106
references.pmid: 23300597
references.citation: Nanomedicine (Lond). 2008 Dec;3(6):761-76
references.pmid: 19025451
references.citation: Int J Oncol. 2007 Aug;31(2):277-83
references.pmid: 17611683
references.citation: Mol Cancer Ther. 2008 Mar;7(3):464-73
references.pmid: 18347134
references.citation: Mol Cell Biochem. 2011 Apr;350(1-2):207-13
references.pmid: 21197560
references.citation: Oncogene. 2006 Aug 7;25(34):4798-811
references.pmid: 16892092
references.citation: Nat Biotechnol. 2005 Aug;23(8):1002-7
references.pmid: 16041363
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):131-42
references.pmid: 16493418
references.citation: Oncogenesis. 2013 Apr 08;2:e42
references.pmid: 23567619
references.citation: Oncogene. 2014 May 22;33(21):2790-800
references.pmid: 23770851
references.citation: PLoS One. 2013 Sep 30;8(9):e75885
references.pmid: 24098737
references.citation: Cancer Res. 2005 Jul 15;65(14):6207-19
references.pmid: 16024622
references.citation: Drug Resist Updat. 2010 Aug-Oct;13(4-5):109-18
references.pmid: 20692200
references.citation: J Urol. 2001 Jan;165(1):130-5
references.pmid: 11125381
references.citation: Nat Rev Cancer. 2002 Jan;2(1):48-58
references.pmid: 11902585
references.citation: Prostate. 2012 Jul 1;72(10):1093-103
references.pmid: 22127852
references.citation: Cell Mol Life Sci. 2009 May;66(10):1682-99
references.pmid: 19153653
references.citation: Onkologie. 2003 Apr;26(2):175-81
references.pmid: 12771527
references.citation: Dev Cell. 2006 Oct;11(4):441-50
references.pmid: 17011485
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19983-8
references.pmid: 18056640
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: J Cell Biochem. 2013 Jul;114(7):1606-15
references.pmid: 23355420
references.citation: Cell Signal. 2013 Dec;25(12):2693-701
references.pmid: 24018051
references.citation: Prostate. 2007 Jun 15;67(9):955-67
references.pmid: 17440963
references.citation: Oncogene. 2003 Oct 20;22(47):7340-58
references.pmid: 14576842
references.citation: Prostate. 2013 Mar;73(4):346-54
references.pmid: 22887127
references.citation: Sci Rep. 2013;3:2687
references.pmid: 24045437
references.citation: Ther Adv Med Oncol. 2012 Nov;4(6):329-40
references.pmid: 23118808
references.citation: Cancer Res. 2009 Aug 15;69(16):6704-12
references.pmid: 19654291
references.citation: Cancer Res. 2009 Sep 15;69(18):7165-9
references.pmid: 19738047
references.citation: J Mammary Gland Biol Neoplasia. 2010 Jun;15(2):235-52
references.pmid: 20521089
references.citation: J Biol Chem. 2010 Jun 18;285(25):19076-84
references.pmid: 20406806
references.citation: Cancer Res. 2009 Mar 15;69(6):2400-7
references.pmid: 19276344
references.citation: Int J Mol Sci. 2013 Jun 05;14(6):11981-93
references.pmid: 23739676
references.citation: Oncol Rep. 2013 Sep;30(3):1113-8
references.pmid: 23807572
references.citation: PLoS One. 2013;8(3):e58929
references.pmid: 23554959
references.citation: Mol Pharmacol. 2009 Jun;75(6):1374-9
references.pmid: 19270061
references.citation: Urol Oncol. 2009 May-Jun;27(3):307-11
references.pmid: 19414119
references.citation: Lancet Oncol. 2013 Feb;14(2):117-24
references.pmid: 23294853
references.citation: Expert Opin Drug Deliv. 2012 Dec;9(12):1443-7
references.pmid: 22954290
references.citation: J Clin Invest. 2009 Jun;119(6):1429-37
references.pmid: 19487819
references.citation: N Engl J Med. 2004 Oct 7;351(15):1513-20
references.pmid: 15470214
references.citation: J Biol Chem. 2007 Jan 26;282(4):2135-43
references.pmid: 17135249
references.citation: Cancer Res. 2008 Apr 1;68(7):2391-9
references.pmid: 18381447
references.citation: J Nutr Biochem. 2010 Feb;21(2):140-6
references.pmid: 19269153
references.citation: Small. 2009 Dec;5(23):2673-7
references.pmid: 19780069
references.citation: Cancer Res. 2011 Mar 1;71(5):1956-67
references.pmid: 21343391
references.citation: Nat Biotechnol. 2010 Feb;28(2):172-6
references.pmid: 20081866
references.citation: RNA. 2008 Mar;14(3):417-24
references.pmid: 18174313
references.citation: Biochem Biophys Res Commun. 2009 Jun 5;383(3):280-5
references.pmid: 19302977
references.citation: PLoS One. 2012;7(3):e32832
references.pmid: 22479342
references.citation: Biomacromolecules. 2012 Mar 12;13(3):664-75
references.pmid: 22288825
references.citation: J Surg Res. 2013 Jul;183(1):296-303
references.pmid: 23199550
references.citation: PLoS One. 2011;6(5):e20341
references.pmid: 21647377
references.citation: Biochem Pharmacol. 2010 Mar 15;79(6):817-24
references.pmid: 19883630
references.citation: Cancer Metastasis Rev. 2012 Dec;31(3-4):653-62
references.pmid: 22684369
references.citation: Prostate Cancer Prostatic Dis. 2000 Aug;3(2):66-75
references.pmid: 12497102
references.citation: PLoS One. 2012;7(12):e51655
references.pmid: 23272133
references.citation: Mol Cell Biochem. 2013 May;377(1-2):121-30
references.pmid: 23417242
references.citation: Pharm Res. 2011 Dec;28(12):2996-3015
references.pmid: 22033880
references.citation: Bioconjug Chem. 2013 Mar 20;24(3):314-32
references.pmid: 23305315
references.citation: Cancer Lett. 2011 Nov 28;310(2):160-9
references.pmid: 21802841
references.citation: Am J Pathol. 2012 Dec;181(6):2188-201
references.pmid: 23041061
references.citation: IUBMB Life. 2007 Dec;59(12):752-7
references.pmid: 18085475
references.citation: Biochem Pharmacol. 2008 Sep 1;76(5):582-8
references.pmid: 18619946
references.citation: Life Sci. 2010 Apr 24;86(17-18):631-7
references.pmid: 20159023
references.citation: Cell. 2009 Nov 25;139(5):871-90
references.pmid: 19945376
references.citation: Carcinogenesis. 2013 Mar;34(3):530-8
references.pmid: 23188675
references.citation: Oncogene. 2010 Aug 26;29(34):4741-51
references.pmid: 20531305
references.citation: Mol Ther. 2012 Jul;20(7):1298-304
references.pmid: 22525514
references.citation: Prostate. 2010 Oct 1;70(14):1501-12
references.pmid: 20687223
references.citation: Prostate. 2012 Aug 1;72(11):1171-8
references.pmid: 22161865
references.citation: J Mol Cell Biol. 2011 Feb;3(1):44-50
references.pmid: 21278451
references.citation: Cancer Res. 2003 May 15;63(10):2492-8
references.pmid: 12750271
references.citation: Nat Mater. 2006 Oct;5(10):791-6
references.pmid: 16998471
references.citation: Nature. 2004 Sep 16;431(7006):350-5
references.pmid: 15372042
references.citation: Int J Cancer. 2012 Apr 15;130(8):1787-97
references.pmid: 21618519
references.citation: Oncogene. 2014 Jun 19;33(25):3334-41
references.pmid: 23873022
references.citation: PLoS One. 2010 Apr 28;5(4):e10365
references.pmid: 20442777
references.citation: Cell Death Dis. 2010 Dec 09;1:e105
references.pmid: 21368878
references.citation: Nucleic Acid Ther. 2012 Dec;22(6):380-90
references.pmid: 23181701
references.citation: Biosens Bioelectron. 2013 Jan 15;39(1):296-9
references.pmid: 22857905
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Nat Med. 2008 Nov;14(11):1271-7
references.pmid: 18931683
references.citation: Stem Cells. 2009 Aug;27(8):1712-21
references.pmid: 19544444
references.citation: Mol Ther. 2013 May;21(5):973-85
references.pmid: 23439496
references.citation: Nature. 2013 Mar 21;495(7441):384-8
references.pmid: 23446346
references.citation: Oncogene. 2013 Aug 29;32(35):4130-8
references.pmid: 23069658
references.citation: J Biol Chem. 2012 Jan 6;287(2):1527-37
references.pmid: 22128178
references.citation: Mol Cancer Ther. 2012 May;11(5):1166-73
references.pmid: 22402125
references.citation: Oncogene. 2006 Mar 16;25(12):1696-708
references.pmid: 16449977
references.citation: Adapt Phys Activ Q. 2009 Oct;26(4):307-20
references.pmid: 19893069
references.citation: Cancer Res. 2007 Jul 15;67(14):6796-805
references.pmid: 17638891
references.citation: J Biol Chem. 2009 Sep 25;284(39):26533-46
references.pmid: 19633292
references.citation: Methods Mol Biol. 2011;676:211-23
references.pmid: 20931400
references.citation: Cancer Res. 2011 Sep 15;71(18):5950-4
references.pmid: 21917736
references.citation: Prostate. 2013 Jul;73(10):1048-56
references.pmid: 23389960
references.citation: Gynecol Oncol. 2010 Oct;119(1):125-30
references.pmid: 20624637
references.citation: BJU Int. 2005 Nov;96(7):985-9
references.pmid: 16225513
references.citation: J Cell Mol Med. 2011 Oct;15(10):2164-75
references.pmid: 21070600
references.citation: Prostate. 2009 Sep 15;69(13):1448-59
references.pmid: 19496068
references.citation: Oncogene. 2013 Jan 17;32(3):296-306
references.pmid: 22370643
references.citation: J Biol Chem. 1989 Jan 15;264(2):862-6
references.pmid: 2492020
references.citation: PLoS One. 2013 Apr 09;8(4):e61064
references.pmid: 23585871
references.citation: Mol Cancer Ther. 2008 Jul;7(7):2152-9
references.pmid: 18645025
references.citation: Cell Cycle. 2008 Aug 15;7(16):2591-600
references.pmid: 18719384
references.citation: Urology. 1997 Jul;50(1):93-9
references.pmid: 9218025
references.citation: Am J Transl Res. 2012;4(4):432-42
references.pmid: 23145211
references.citation: Cancer Res. 2012 Jul 1;72(13):3393-404
references.pmid: 22719071