Abstract
Noncoding RNAs have emerged as key regulators of the genome upon gene expression profiling and genome-wide sequencing. Among these noncoding RNAs, microRNAs are short noncoding RNAs that regulate a plethora of functions, biological processes and human diseases by targeting the messenger RNA stability through 3’UTR binding, leading to either mRNA cleavage or translation repression, depending on microRNA-mRNA complementarity degree. Additionally, strong evidence has suggested that dysregulation of miRNAs contributes to the etiology and progression of human cancers, such as lung cancer, the most common and deadliest cancer worldwide. Indeed, by acting as oncogenes or tumor suppressors, microRNAs control all aspects of lung cancer malignancy, including cell proliferation, survival, migration, invasion, angiogenesis, cancer stem cells, immune-surveillance escape, and therapy resistance; and their expressions are often associated with clinical parameters. Moreover, several deregulated microRNAs in lung cancer are carried by exosomes and microvesicles and secreted in body fluids, mainly the circulation, where they conserve their stable forms. Subsequently, seminal efforts have been focused on extracellular microRNAs levels as noninvasive diagnostic and prognostic biomarkers in lung cancer. In this review, focusing on recent literature, we summarize the deregulation, mechanisms of action, functions and highlight clinical applications of miRNAs for better management and design of future lung cancer targeted therapies.
Keywords: miRNAs, lung cancer, NSCLC, immune response, therapeutics, key regulations.
[http://dx.doi.org/10.21037/tlcr.2018.05.06] [PMID: 30050761]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1016/j.soc.2016.02.001] [PMID: 27261907]
[http://dx.doi.org/10.1016/j.currproblcancer.2017.07.002] [PMID: 28823540]
[PMID: 24163741]
[http://dx.doi.org/10.1002/cam4.2183] [PMID: 31016879]
[PMID: 26389304]
[http://dx.doi.org/10.18632/oncotarget.20955] [PMID: 29113423]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01707.x] [PMID: 20735434]
[http://dx.doi.org/10.1016/j.ccr.2006.01.025] [PMID: 16530703]
[http://dx.doi.org/10.15586/codon.glioblastoma.2017.ch6]
[http://dx.doi.org/10.1073/pnas.0307323101] [PMID: 14973191]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1083] [PMID: 17699775]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-2352] [PMID: 16266980]
[http://dx.doi.org/10.1038/s41598-019-39453-2] [PMID: 30816202]
[http://dx.doi.org/10.1111/cpr.12394] [PMID: 28990243]
[http://dx.doi.org/10.1038/srep16901] [PMID: 26582602]
[http://dx.doi.org/10.1371/journal.pone.0125026] [PMID: 25965386]
[http://dx.doi.org/10.4161/cbt.26370] [PMID: 24025412]
[http://dx.doi.org/10.3892/mmr.2013.1517] [PMID: 23759980]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-2638] [PMID: 20068099]
[http://dx.doi.org/10.1200/JCO.2008.19.4134] [PMID: 19273703]
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1736] [PMID: 20068076]
[http://dx.doi.org/10.1097/JTO.0000000000000423] [PMID: 25695220]
[http://dx.doi.org/10.1158/0008-5472.CAN-11-1020] [PMID: 21856745]
[http://dx.doi.org/10.1002/ijc.26153] [PMID: 21544802]
[http://dx.doi.org/10.1002/ijc.26177] [PMID: 21557218]
[http://dx.doi.org/10.1186/s12931-014-0149-3] [PMID: 25421010]
[http://dx.doi.org/10.1371/journal.pone.0134220] [PMID: 26237047]
[http://dx.doi.org/10.1002/cam4.1490] [PMID: 29673101]
[PMID: 31938391]
[PMID: 31938164]
[http://dx.doi.org/10.2147/CMAR.S232383] [PMID: 32021461]
[http://dx.doi.org/10.1155/2020/7415909] [PMID: 31976313]
[http://dx.doi.org/10.1373/clinchem.2007.101741] [PMID: 18719201]
[http://dx.doi.org/10.3892/or.2014.3029] [PMID: 24549225]
[http://dx.doi.org/10.3109/07357907.2014.922569] [PMID: 24945821]
[http://dx.doi.org/10.3892/ijmm.2015.2388] [PMID: 26497897]
[http://dx.doi.org/10.18632/oncotarget.3255] [PMID: 25840419]
[http://dx.doi.org/10.4149/neo_2017_317] [PMID: 28253725]
[http://dx.doi.org/10.18632/oncotarget.11198] [PMID: 27517633]
[PMID: 31938373]
[PMID: 29863251]
[http://dx.doi.org/10.1016/j.bbrc.2013.07.123] [PMID: 23939044]
[http://dx.doi.org/10.1371/journal.pone.0064759] [PMID: 23734217]
[http://dx.doi.org/10.3892/mmr.2015.4163] [PMID: 26238532]
[http://dx.doi.org/10.3892/mmr.2016.5421] [PMID: 27356635]
[http://dx.doi.org/10.1007/s13277-014-2972-z] [PMID: 25524579]
[http://dx.doi.org/10.1007/s13277-015-4150-3] [PMID: 26432332]
[http://dx.doi.org/10.3892/or.2013.2755] [PMID: 24084898]
[http://dx.doi.org/10.18632/oncotarget.4972] [PMID: 26317552]
[PMID: 26097565]
[http://dx.doi.org/10.1186/s13046-015-0169-y] [PMID: 26063204]
[http://dx.doi.org/10.1016/j.cca.2010.02.074] [PMID: 20223231]
[http://dx.doi.org/10.1016/j.biopha.2018.01.076] [PMID: 29665655]
[http://dx.doi.org/10.1073/pnas.1500886112] [PMID: 26124099]
[http://dx.doi.org/10.1007/s00432-014-1836-7] [PMID: 25245053]
[http://dx.doi.org/10.1159/000479207] [PMID: 28715819]
[http://dx.doi.org/10.3892/ijo.2017.3999] [PMID: 28534966]
[http://dx.doi.org/10.1186/s40064-016-3425-5] [PMID: 27795904]
[http://dx.doi.org/10.4252/wjsc.v7.i8.1078] [PMID: 26435768]
[http://dx.doi.org/10.1007/s13277-014-2158-8] [PMID: 24903381]
[http://dx.doi.org/10.1016/j.jconrel.2012.01.014] [PMID: 22285547]
[http://dx.doi.org/10.1002/mc.22221] [PMID: 25252218]
[http://dx.doi.org/10.1016/j.biopha.2011.09.013] [PMID: 22301433]
[http://dx.doi.org/10.1172/JCI61271] [PMID: 23426183]
[http://dx.doi.org/10.1016/j.canlet.2018.04.022] [PMID: 29702194]
[http://dx.doi.org/10.1089/cell.2017.0045] [PMID: 29620443]
[http://dx.doi.org/10.1038/cddis.2017.544] [PMID: 29072692]
[http://dx.doi.org/10.1016/j.lungcan.2015.11.013] [PMID: 26711929]
[http://dx.doi.org/10.3892/or.2012.2095] [PMID: 23117485]
[http://dx.doi.org/10.1371/journal.pone.0090022] [PMID: 24595209]
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[http://dx.doi.org/10.2174/1566523214666141224100612] [PMID: 25537774]
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[http://dx.doi.org/10.1097/JTO.0b013e318299ac32] [PMID: 23945385]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0577] [PMID: 28606918]
[http://dx.doi.org/10.3892/ol.2017.5569] [PMID: 28454243]
[http://dx.doi.org/10.1159/000487006] [PMID: 29533963]
[http://dx.doi.org/10.18632/oncotarget.14369] [PMID: 28055956]
[PMID: 28678319]
[http://dx.doi.org/10.18632/oncotarget.15009] [PMID: 28178672]
[http://dx.doi.org/10.1038/onc.2017.105] [PMID: 28436951]
[http://dx.doi.org/10.1111/jcmm.13056] [PMID: 28026121]
[http://dx.doi.org/10.1038/s41598-017-15475-6] [PMID: 29127370]
[http://dx.doi.org/10.1186/s12943-019-0959-5] [PMID: 30866952]
[http://dx.doi.org/10.3892/or.2016.4797] [PMID: 29138862]
[http://dx.doi.org/10.1016/j.canlet.2013.08.030] [PMID: 23981581]
[http://dx.doi.org/10.1007/s13277-014-2861-5] [PMID: 25501507]
[http://dx.doi.org/10.1007/s13277-015-3247-z] [PMID: 25716201]
[http://dx.doi.org/10.1038/mtna.2016.96] [PMID: 27845771]
[http://dx.doi.org/10.3892/ijo.2016.3637] [PMID: 27498924]
[http://dx.doi.org/10.1016/j.biopha.2017.07.005] [PMID: 28738500]
[http://dx.doi.org/10.3892/or.2017.5619] [PMID: 28498463]
[http://dx.doi.org/10.3892/or.2017.5885] [PMID: 28791372]
[PMID: 26261507]
[http://dx.doi.org/10.1007/s13277-015-3550-8] [PMID: 25983004]
[http://dx.doi.org/10.1016/j.bbrc.2016.08.001] [PMID: 27495872]
[http://dx.doi.org/10.3892/mmr.2017.6100] [PMID: 28075452]
[http://dx.doi.org/10.3892/ijmm.2015.2071] [PMID: 25604748]
[http://dx.doi.org/10.18632/oncotarget.14298] [PMID: 28035073]
[http://dx.doi.org/10.1073/pnas.1520329112] [PMID: 26627242]
[http://dx.doi.org/10.1038/nm.2890] [PMID: 22863786]
[http://dx.doi.org/10.1002/path.1706] [PMID: 15641020]
[http://dx.doi.org/10.1002/cncr.26560] [PMID: 22139708]
[http://dx.doi.org/10.1016/j.canlet.2011.11.024] [PMID: 22120675]
[http://dx.doi.org/10.1371/journal.pone.0072615] [PMID: 23991130]
[http://dx.doi.org/10.1371/journal.pone.0095716] [PMID: 24755562]
[http://dx.doi.org/10.1093/abbs/gms026] [PMID: 22510476]
[http://dx.doi.org/10.1371/journal.pone.0039167] [PMID: 22723956]
[PMID: 24400442]
[http://dx.doi.org/10.3892/ijmm.2013.1439] [PMID: 23856992]
[http://dx.doi.org/10.1016/j.bbrc.2013.09.111] [PMID: 24099768]
[http://dx.doi.org/10.1016/j.canlet.2013.09.034] [PMID: 24099915]
[http://dx.doi.org/10.1186/1746-1596-9-143] [PMID: 25012722]
[http://dx.doi.org/10.1186/1476-4598-13-193] [PMID: 25128483]
[http://dx.doi.org/10.1038/bjc.2014.157] [PMID: 24921914]
[http://dx.doi.org/10.3892/mmr.2014.2688] [PMID: 25339370]
[http://dx.doi.org/10.1038/cgt.2014.73] [PMID: 25721211]
[http://dx.doi.org/10.1016/j.cellsig.2015.04.009] [PMID: 25917317]
[http://dx.doi.org/10.1016/j.yexmp.2014.04.008] [PMID: 24769353]
[http://dx.doi.org/10.1016/j.bbrc.2014.02.073] [PMID: 24582749]
[http://dx.doi.org/10.1016/j.lungcan.2019.07.005] [PMID: 31447008]
[http://dx.doi.org/10.1016/j.omtn.2019.04.027] [PMID: 31163321]
[http://dx.doi.org/10.3892/ijo.2012.1535] [PMID: 22752005]
[http://dx.doi.org/10.1172/JCI76561] [PMID: 25347474]
[http://dx.doi.org/10.1016/j.bbrc.2015.02.003] [PMID: 25677619]
[http://dx.doi.org/10.1016/j.lungcan.2018.02.002] [PMID: 29571988]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6460] [PMID: 18632605]
[http://dx.doi.org/10.3892/or.2018.6439] [PMID: 29767245]
[http://dx.doi.org/10.1186/s13046-019-1027-0] [PMID: 30736829]
[http://dx.doi.org/10.7150/ijms.44377] [PMID: 32308549]