Abstract
Background: Breast cancer (BC), as a heterogenous disease, is the most common cancer among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive and malignant subtype with a poor prognosis and a high rate of relapse and metastasis that is closely linked to epithelial–mesenchymal transition (EMT). It is well-documented that miRNAs play oncogenic (oncomiR) or tumor-suppressive (TS-miR) roles in controlling apoptosis (apoptomiR), differentiation, cell proliferation, invasion, migration, etc. Regarding the regulatory roles of miRNAs in the expression levels of various genes, dysfunction or deregulated expression of these molecules can lead to various disorders, including various types of cancers, such as BC. Many miRNAs have been identified with critical contributions in the initiation and development of different types of BCs due to their influence on the p53 signaling network.
Objective: The aim of this review was to discuss several important deregulated miRNAs that are involved in the p53 signaling pathway in BC, especially the TNBC subtype. Finally, miRNAs’ involvement in tumor properties and their applications as diagnostic, prognostic, and therapeutic agents have been elaborated in detail.
Results: The miRNA expression profile of BC is involved in tumor-grade estrogen receptor (ER) and progesterone receptor (PR) expression, and other pathological properties from luminal A to TNBC/basal-like subtypes via p53 signaling pathways.
Conclusion: Developing our knowledge about miRNA expression profile in BC, as well as molecular mechanisms of initiation and progression of BC can help to find new prognostic, diagnostic, and therapeutic biomarkers, which can lead to a suitable treatment for BC patients.
Keywords: Triple-negative breast cancer, MiRNA, P53, Biomarker, Drug resistance.
[http://dx.doi.org/10.3390/cancers13153691] [PMID: 34359591]
[http://dx.doi.org/10.48095/ccko2021382] [PMID: 34702045]
[http://dx.doi.org/10.9734/air/2023/v24i4943]
[http://dx.doi.org/10.1016/j.amsu.2019.11.021] [PMID: 31890196]
[http://dx.doi.org/10.1093/annonc/mdv221] [PMID: 25939896]
[http://dx.doi.org/10.1093/annonc/mdt303] [PMID: 23917950]
[http://dx.doi.org/10.1038/s41418-018-0103-x] [PMID: 29666469]
[http://dx.doi.org/10.1016/j.humpath.2017.08.026] [PMID: 28882698]
[http://dx.doi.org/10.1016/j.canlet.2016.03.001] [PMID: 26965997]
[PMID: 35463822]
[http://dx.doi.org/10.5812/semj.94641]
[http://dx.doi.org/10.1371/journal.pone.0191195] [PMID: 29324832]
[http://dx.doi.org/10.1038/jhg.2016.89] [PMID: 27439682]
[http://dx.doi.org/10.1007/978-1-4939-9207-2_4]
[http://dx.doi.org/10.1093/cvr/cvz302] [PMID: 31782762]
[http://dx.doi.org/10.1093/nar/gky1141] [PMID: 30423142]
[http://dx.doi.org/10.1038/s41592-021-01385-z] [PMID: 35017737]
[http://dx.doi.org/10.2174/1381612826666200504120737] [PMID: 32364067]
[http://dx.doi.org/10.1038/s41477-021-01000-1] [PMID: 34593993]
[http://dx.doi.org/10.1002/wrna.1680] [PMID: 34155810]
[http://dx.doi.org/10.3892/ijmm.2015.2123] [PMID: 25738546]
[http://dx.doi.org/10.1002/jcb.25609] [PMID: 27216701]
[http://dx.doi.org/10.1016/j.molonc.2012.09.006] [PMID: 23102669]
[http://dx.doi.org/10.1002/jbt.22567] [PMID: 32729651]
[http://dx.doi.org/10.1038/onc.2011.444] [PMID: 21963843]
[http://dx.doi.org/10.1007/s00432-018-2689-2] [PMID: 29923083]
[http://dx.doi.org/10.1089/omi.2018.0157] [PMID: 30388053]
[http://dx.doi.org/10.1016/j.semcancer.2020.09.002]
[http://dx.doi.org/10.1002/ijc.27767] [PMID: 22886769]
[PMID: 35959860]
[http://dx.doi.org/10.1038/s41467-017-01713-y] [PMID: 29170488]
[http://dx.doi.org/10.3390/cells11030572] [PMID: 35159383]
[http://dx.doi.org/10.1101/2020.05.05.078014]
[http://dx.doi.org/10.1038/s41540-019-0115-2] [PMID: 31754458]
[http://dx.doi.org/10.1186/bcr1867] [PMID: 18373886]
[http://dx.doi.org/10.3390/biom10030472] [PMID: 32204575]
[http://dx.doi.org/10.1016/j.ctrv.2018.09.004] [PMID: 30336366]
[http://dx.doi.org/10.1038/onc.2012.305] [PMID: 22797073]
[http://dx.doi.org/10.1101/gad.247452.114] [PMID: 25128494]
[http://dx.doi.org/10.1111/jebm.12428] [PMID: 33988919]
[http://dx.doi.org/10.3892/or.2018.6379] [PMID: 29693179]
[http://dx.doi.org/10.1007/s10549-012-2034-4] [PMID: 22476851]
[http://dx.doi.org/10.1038/ncb1722] [PMID: 18376396]
[http://dx.doi.org/10.4048/jbc.2014.17.2.143] [PMID: 25013435]
[http://dx.doi.org/10.1016/j.molonc.2012.03.003] [PMID: 22578566]
[http://dx.doi.org/10.1016/j.cell.2009.10.014] [PMID: 19878981]
[http://dx.doi.org/10.1016/j.cell.2007.10.054] [PMID: 18083101]
[http://dx.doi.org/10.1089/dna.2013.2132] [PMID: 24684598]
[http://dx.doi.org/10.1093/carcin/bgv087] [PMID: 26088362]
[http://dx.doi.org/10.1007/s13277-015-3275-8] [PMID: 25731732]
[http://dx.doi.org/10.1093/carcin/bgs383] [PMID: 23250910]
[http://dx.doi.org/10.1007/s12032-014-0057-x] [PMID: 24930006]
[http://dx.doi.org/10.1261/rna.1034808] [PMID: 18812439]
[http://dx.doi.org/10.1158/0008-5472.CAN-16-0140] [PMID: 27402080]
[http://dx.doi.org/10.1007/s10549-014-3069-5] [PMID: 25086633]
[http://dx.doi.org/10.1038/onc.2013.322] [PMID: 23955085]
[http://dx.doi.org/10.1097/CAD.0000000000000296] [PMID: 26398931]
[http://dx.doi.org/10.1038/onc.2013.26] [PMID: 23416982]
[http://dx.doi.org/10.1002/emmm.201100136] [PMID: 21472990]
[http://dx.doi.org/10.3892/etm.2018.5945] [PMID: 29731835]
[http://dx.doi.org/10.1038/onc.2014.363] [PMID: 25417703]
[http://dx.doi.org/10.1371/journal.pone.0048474] [PMID: 23144891]
[http://dx.doi.org/10.1093/carcin/bgu202] [PMID: 25239643]
[http://dx.doi.org/10.1186/s12885-016-2620-7] [PMID: 27484639]
[http://dx.doi.org/10.1002/gcc.22422] [PMID: 27717206]
[PMID: 29771420]
[http://dx.doi.org/10.7314/APJCP.2016.17.4.1887] [PMID: 27221871]
[http://dx.doi.org/10.3892/mmr.2014.2222] [PMID: 24821285]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-3559] [PMID: 19190326]
[http://dx.doi.org/10.1158/0008-5472.CAN-14-2108] [PMID: 25712342]
[http://dx.doi.org/10.1007/s13277-016-5361-y] [PMID: 27696295]
[http://dx.doi.org/10.3390/ncrna8010005] [PMID: 35076579]
[http://dx.doi.org/10.1016/j.ajpath.2014.08.020] [PMID: 25440114]
[http://dx.doi.org/10.1038/modpathol.2012.244] [PMID: 23392436]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-1699] [PMID: 23536562]
[http://dx.doi.org/10.1371/journal.pone.0260327] [PMID: 34797887]
[http://dx.doi.org/10.1016/j.gene.2020.144453] [PMID: 32035242]
[http://dx.doi.org/10.1038/onc.2008.72] [PMID: 18372920]
[PMID: 28386324]
[http://dx.doi.org/10.1016/j.biopha.2015.11.005] [PMID: 26796263]
[http://dx.doi.org/10.3389/fgene.2016.00175] [PMID: 27746811]
[http://dx.doi.org/10.1186/s12885-019-5951-3] [PMID: 31351450]
[http://dx.doi.org/10.3390/ijms22041557] [PMID: 33557112]
[http://dx.doi.org/10.1186/1471-2407-9-163] [PMID: 19473551]
[http://dx.doi.org/10.1007/s10238-014-0332-3] [PMID: 25516467]
[http://dx.doi.org/10.3390/jpm10030098] [PMID: 32842653]
[http://dx.doi.org/10.3390/ijms161226090] [PMID: 26633365]
[http://dx.doi.org/10.1002/jcp.27839] [PMID: 30488443]
[http://dx.doi.org/10.1016/j.mcp.2016.10.005] [PMID: 27725294]
[http://dx.doi.org/10.1016/j.critrevonc.2020.103196] [PMID: 33307198]
[http://dx.doi.org/10.1158/0008-5472.CAN-09-4250] [PMID: 20354188]
[http://dx.doi.org/10.1128/MCB.00941-08] [PMID: 18794355]
[http://dx.doi.org/10.3389/fonc.2020.01415] [PMID: 32903519]
[http://dx.doi.org/10.1098/rstb.2008.0209] [PMID: 19008191]
[http://dx.doi.org/10.1074/jbc.M110.101055] [PMID: 20371610]
[http://dx.doi.org/10.1371/journal.pone.0096228] [PMID: 24788655]
[http://dx.doi.org/10.1007/s13277-015-3263-z] [PMID: 25744731]
[http://dx.doi.org/10.1073/pnas.1110977109] [PMID: 22949650]
[http://dx.doi.org/10.1038/s41598-017-16112-y] [PMID: 29162923]
[http://dx.doi.org/10.1016/j.bbrc.2016.03.069] [PMID: 27003255]
[http://dx.doi.org/10.1038/s41419-020-03327-7] [PMID: 33414456]
[http://dx.doi.org/10.1371/journal.pone.0047709] [PMID: 23112837]
[http://dx.doi.org/10.1038/ncb2173] [PMID: 21336307]
[http://dx.doi.org/10.1158/1541-7786.MCR-21-0098] [PMID: 34312289]
[http://dx.doi.org/10.1002/iub.1273] [PMID: 24846313]
[http://dx.doi.org/10.1111/nep.13394] [PMID: 29717517]
[http://dx.doi.org/10.1080/15384101.2018.1489176] [PMID: 29954239]
[http://dx.doi.org/10.1093/carcin/bgu175] [PMID: 25123132]
[http://dx.doi.org/10.1002/wrna.1533] [PMID: 30895717]
[http://dx.doi.org/10.1007/s12253-017-0188-4] [PMID: 28101798]
[http://dx.doi.org/10.1038/onc.2008.171] [PMID: 18504431]
[http://dx.doi.org/10.3892/or.2016.4788] [PMID: 27175941]
[http://dx.doi.org/10.1186/s12929-020-00693-4] [PMID: 33248456]
[http://dx.doi.org/10.1186/1479-5876-11-57] [PMID: 23497265]
[http://dx.doi.org/10.7150/jca.25576] [PMID: 30405848]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2321] [PMID: 26676753]
[http://dx.doi.org/10.1038/mt.2012.201] [PMID: 23032974]
[http://dx.doi.org/10.1016/j.jrras.2022.08.001]
[http://dx.doi.org/10.1016/j.biomaterials.2014.02.006] [PMID: 24565525]
[http://dx.doi.org/10.4161/cc.7.16.6533] [PMID: 18719384]
[http://dx.doi.org/10.1038/cdd.2009.56] [PMID: 19461653]
[http://dx.doi.org/10.18632/oncotarget.15214] [PMID: 28423483]
[http://dx.doi.org/10.4161/cc.10.24.18552] [PMID: 22134354]
[http://dx.doi.org/10.1002/jcp.25245] [PMID: 26553365]
[http://dx.doi.org/10.1016/j.gene.2016.07.055] [PMID: 27461945]
[http://dx.doi.org/10.3349/ymj.2019.60.4.336] [PMID: 30900419]
[http://dx.doi.org/10.3390/ijms22010027] [PMID: 33375067]
[http://dx.doi.org/10.4161/cc.10.3.14754] [PMID: 21270527]
[http://dx.doi.org/10.3892/ijo.2016.3573] [PMID: 27278159]
[http://dx.doi.org/10.1158/1538-7445.AM2018-26]
[http://dx.doi.org/10.1038/onc.2013.53] [PMID: 23474752]
[http://dx.doi.org/10.1038/cr.2009.18] [PMID: 19238171]
[http://dx.doi.org/10.3390/ncrna5040053] [PMID: 31752366]
[http://dx.doi.org/10.1038/modpathol.2016.38] [PMID: 26916073]
[http://dx.doi.org/10.1038/cddis.2014.249]
[http://dx.doi.org/10.1186/1471-2407-14-51] [PMID: 24479446]
[http://dx.doi.org/10.2174/2211536611201010065] [PMID: 25048092]
[http://dx.doi.org/10.1186/1476-4598-13-115] [PMID: 29304823]
[http://dx.doi.org/10.1371/journal.pone.0049636] [PMID: 23166734]
[http://dx.doi.org/10.3747/co.v17i1.356] [PMID: 20179807]
[http://dx.doi.org/10.1186/s12943-015-0458-2] [PMID: 26536864]
[http://dx.doi.org/10.1111/cpr.12534] [PMID: 30338598]
[http://dx.doi.org/10.1016/j.cell.2010.05.017] [PMID: 20603000]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2011] [PMID: 25547678]
[http://dx.doi.org/10.1016/j.abb.2020.108326] [PMID: 32142889]
[http://dx.doi.org/10.1016/j.biopha.2017.02.028] [PMID: 28320108]
[http://dx.doi.org/10.14715/cmb/2021.67.3.2] [PMID: 34933738]
[PMID: 33764337]
[http://dx.doi.org/10.1172/JCI45390] [PMID: 21841313]
[http://dx.doi.org/10.1166/jbt.2022.3018]
[http://dx.doi.org/10.3390/cancers15010288] [PMID: 36612285]
[http://dx.doi.org/10.1016/j.celrep.2018.07.010] [PMID: 30089260]
[http://dx.doi.org/10.1177/1947601911429743] [PMID: 22393463]
[http://dx.doi.org/10.1128/JVI.00703-10] [PMID: 20702634]
[http://dx.doi.org/10.3892/ijo.2015.3178] [PMID: 26397233]
[http://dx.doi.org/10.3892/ijo.2013.2059] [PMID: 23939688]
[http://dx.doi.org/10.1186/1471-2407-12-445] [PMID: 23031797]
[http://dx.doi.org/10.1158/1541-7786.MCR-13-0312-T] [PMID: 24324033]
[http://dx.doi.org/10.1371/journal.pone.0064273] [PMID: 23717581]
[http://dx.doi.org/10.1186/s12935-018-0642-8] [PMID: 30386180]
[http://dx.doi.org/10.1016/j.bbrc.2016.05.031] [PMID: 27166155]
[http://dx.doi.org/10.1038/onc.2013.597] [PMID: 24469051]
[http://dx.doi.org/10.1371/journal.pone.0143993] [PMID: 26657485]
[http://dx.doi.org/10.1038/s41419-018-0628-4] [PMID: 29844410]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2132] [PMID: 19318481]
[http://dx.doi.org/10.1038/nm.2459] [PMID: 21946536]
[http://dx.doi.org/10.1093/carcin/bgq184] [PMID: 20810544]
[http://dx.doi.org/10.1007/s10549-011-1905-4] [PMID: 22167321]
[http://dx.doi.org/10.1038/nm.2645] [PMID: 22388088]
[http://dx.doi.org/10.1038/jhg.2010.4] [PMID: 20150920]
[http://dx.doi.org/10.1016/j.humpath.2017.08.026]
[http://dx.doi.org/10.1038/onc.2011.54] [PMID: 21460854]
[http://dx.doi.org/10.1186/1471-2164-14-643] [PMID: 24059244]
[http://dx.doi.org/10.1073/pnas.1402604111] [PMID: 24616504]
[http://dx.doi.org/10.1101/gad.233585.113] [PMID: 24532687]
[http://dx.doi.org/10.1038/ncb2024] [PMID: 20173740]
[http://dx.doi.org/10.1007/s13277-015-4605-6] [PMID: 26676637]
[http://dx.doi.org/10.1080/21691401.2019.1638791] [PMID: 31284781]
[http://dx.doi.org/10.1371/journal.pone.0158946] [PMID: 27404381]
[http://dx.doi.org/10.18632/oncotarget.15520] [PMID: 28423566]
[http://dx.doi.org/10.3390/diagnostics12040789] [PMID: 35453838]
[http://dx.doi.org/10.1634/theoncologist.2010-0103] [PMID: 20576643]
[http://dx.doi.org/10.1186/1471-2407-14-448] [PMID: 24938880]
[http://dx.doi.org/10.1093/abbs/gmz021] [PMID: 30839051]
[http://dx.doi.org/10.1038/onc.2012.636] [PMID: 23353819]
[http://dx.doi.org/10.1097/MD.0000000000007085] [PMID: 28562579]
[http://dx.doi.org/10.1096/fj.201800120R] [PMID: 29812973]
[http://dx.doi.org/10.1186/bcr2766] [PMID: 21047409]
[http://dx.doi.org/10.18632/oncotarget.10485] [PMID: 27409424]
[http://dx.doi.org/10.1186/s40169-019-0240-y] [PMID: 31468250]
[http://dx.doi.org/10.1111/jcmm.12522] [PMID: 25702703]
[http://dx.doi.org/10.4048/jbc.2011.14.4.269] [PMID: 22323912]
[http://dx.doi.org/10.1074/jbc.M110.216887] [PMID: 21471222]
[http://dx.doi.org/10.1177/153303461000900109] [PMID: 20082533]
[http://dx.doi.org/10.3390/cancers12113298] [PMID: 33171872]
[http://dx.doi.org/10.1517/14728222.2015.1069816] [PMID: 26189482]
[http://dx.doi.org/10.3390/cells8121492] [PMID: 31766744]
[http://dx.doi.org/10.1021/acsnano.5b02471] [PMID: 26387848]
[http://dx.doi.org/10.1016/j.ymthe.2019.04.018] [PMID: 31085078]
[http://dx.doi.org/10.1021/nn507465d] [PMID: 25652012]
[http://dx.doi.org/10.7314/APJCP.2013.14.4.2361] [PMID: 23725141]
[http://dx.doi.org/10.1155/2011/696208]
[http://dx.doi.org/10.1007/s13277-015-3844-x] [PMID: 26298722]
[http://dx.doi.org/10.1002/ddr.21275] [PMID: 26310899]
[http://dx.doi.org/10.3892/or.2015.4417] [PMID: 26572075]
[http://dx.doi.org/10.1186/s13148-018-0587-8] [PMID: 30744689]
[http://dx.doi.org/10.1016/j.drudis.2019.09.001] [PMID: 31520748]
[http://dx.doi.org/10.1016/j.biopha.2018.11.122] [PMID: 30529766]
[http://dx.doi.org/10.2174/1871520616666160502122724]
[http://dx.doi.org/10.3389/fonc.2018.00575] [PMID: 30564555]
[http://dx.doi.org/10.1158/2159-8274.CD-10-0028] [PMID: 22039576]
[http://dx.doi.org/10.1186/s12885-017-3457-4] [PMID: 28724364]
[http://dx.doi.org/10.1007/s10549-018-4925-5] [PMID: 30173296]
[http://dx.doi.org/10.1038/s41388-018-0445-3] [PMID: 30093634]
[http://dx.doi.org/10.1016/j.bbrc.2017.05.111] [PMID: 28536076]
[http://dx.doi.org/10.3389/fonc.2021.717759] [PMID: 34760689]
[http://dx.doi.org/10.1007/s40291-020-00447-w] [PMID: 32067191]