miRNA gene miRNA_log2FC miRNA_pvalue gene_log2FC gene_pvalue interactions correlation_beta correlation_pvalue PMID evidence outcome cancer hsa-miR-21-5p ACBD5 1.0504925175311 2.58081295984106e-11 -0.311230529317669 9.09528601484802e-08 miRNAWalker2_validate -0.115153808011155 5.75049986020304e-17 NA NA NA hsa-miR-21-5p ANKRD46 1.0504925175311 2.58081295984106e-11 -0.329751910559951 1.29000734601328e-08 miRNAWalker2_validate;miRTarBase -0.208615410664561 2.34532803031741e-52 21219636 Knockdown of miR-21 significantly increased the expression of ANKRD46 at both mRNA and protein levels; ANKRD46 is newly identified as a direct target of miR-21 in BC breast cancer hsa-miR-21-5p ASRGL1 1.0504925175311 2.58081295984106e-11 -0.323589677024819 1.7174035660774e-07 miRNAWalker2_validate -0.198575585377101 3.42215748803705e-35 NA NA NA hsa-miR-21-5p ATRX 1.0504925175311 2.58081295984106e-11 0.00082443450307057 0.992488330570116 miRNAWalker2_validate -0.105212144122095 4.65569044345593e-05 NA NA NA hsa-miR-21-5p AUTS2 1.0504925175311 2.58081295984106e-11 -0.0630211320780845 0.29094099874943 miRNAWalker2_validate -0.119950363359054 7.86746208258862e-15 NA NA NA hsa-miR-21-5p BASP1 1.0504925175311 2.58081295984106e-11 -0.486211739382857 6.48040257284722e-07 miRNAWalker2_validate;miRTarBase -0.27569976304215 5.12523309872382e-24 NA NA NA hsa-miR-21-5p CLIP4 1.0504925175311 2.58081295984106e-11 -0.298147304993758 1.35045826050285e-08 miRNAWalker2_validate -0.118135041825582 8.5031918303327e-18 NA NA NA hsa-miR-21-5p CPEB3 1.0504925175311 2.58081295984106e-11 -0.559995199125646 7.28978945175864e-14 miRNAWalker2_validate -0.266929167412625 3.44606061924003e-36 NA NA NA hsa-miR-21-5p DUSP8 1.0504925175311 2.58081295984106e-11 -0.17515174843211 0.0382928021347344 miRNAWalker2_validate -0.22189839167749 7.87221670188543e-20 NA NA NA hsa-miR-21-5p EDIL3 1.0504925175311 2.58081295984106e-11 -0.618192885421041 6.79420434555256e-05 miRNAWalker2_validate -0.122842031565658 0.0117531187001923 NA NA NA hsa-miR-21-5p EGFR 1.0504925175311 2.58081295984106e-11 0.375473556369618 0.0155485714375729 miRNAWalker2_validate;miRTarBase -0.118832377375515 0.0117576517085032 20113523;24012640;20048743;24198203;24331411;26563758;19597153;26026961 Thus the miR-21 inhibitor might interrupt the activity of EGFR pathways independently of PTEN status;Further the expression of miR-21 is regulated by EGFR via the activation of β-catenin and AP-1; These data indicate that a feedback loop exists between miR-21 and EGFR; These results clarify a novel association between miR-21 and EGFR in the regulation of cancer cell progression;Downregulation of miR 21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status;In radically resected NSCLC patients the expression levels of miR-21 10b in patients with EGFR mutation were much higher than those without mutation;MiR 21 overexpression is associated with acquired resistance of EGFR TKI in non small cell lung cancer;Higher expression levels of miR-21 AmiR-27a and miR-218 detected in this study suggest potential roles of these miRNAs in primary resistance to EGFR-TKI in advanced NSCLC patients with EGFR exon 19 deletion mutations;MiR 21 is an EGFR regulated anti apoptotic factor in lung cancer in never smokers; The changes in expression of some of these miRNAs including miR-21 were more remarkable in cases with EGFR mutations than in those without these mutations; In the never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21 antisense inhibition of miR-21 enhanced AG1478-induced apoptosis; In a never-smoker-derived adenocarcinoma cell line H441 with wild-type EGFR the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself; These results suggest that aberrantly increased expression of miR-21 which is enhanced further by the activated EGFR signaling pathway plays a significant role in lung carcinogenesis in never-smokers as well as in smokers and is a potential therapeutic target in both EGFR-mutant and wild-type cases;Nickel may contribute to EGFR mutation and synergistically promotes tumor invasion in EGFR mutated lung cancer via nickel induced microRNA 21 expression ;progression;;;drug resistance;staging;drug resistance;tumorigenesis; glioblastoma;glioblastoma;glioblastoma;lung squamous cell cancer;lung squamous cell cancer;lung squamous cell cancer;lung cancer;lung cancer hsa-miR-21-5p EIF4A2 1.0504925175311 2.58081295984106e-11 -0.232145594809177 0.000245590662312804 miRNAWalker2_validate;miRTarBase -0.108864918862811 3.12505909929246e-18 NA NA NA hsa-miR-21-5p ELAVL4 1.0504925175311 2.58081295984106e-11 -0.637157204078504 4.13366994012396e-05 miRNAWalker2_validate -0.422847361878242 1.87297612718515e-19 NA NA NA hsa-miR-21-5p ELOVL4 1.0504925175311 2.58081295984106e-11 -0.171602182188974 0.0311115856851339 miRNAWalker2_validate -0.176569390786384 1.1443878287098e-13 NA NA NA hsa-miR-21-5p FAM126B 1.0504925175311 2.58081295984106e-11 -0.201740043202993 0.000596653679563337 miRNAWalker2_validate -0.144911711444422 2.68427149707289e-19 NA NA NA hsa-miR-21-5p FBXL17 1.0504925175311 2.58081295984106e-11 -0.225273298130301 6.69535449186666e-06 miRNAWalker2_validate -0.11320956988366 6.33032507767722e-22 NA NA NA hsa-miR-21-5p FMR1 1.0504925175311 2.58081295984106e-11 -0.174989595580888 0.000181875579454969 miRNAWalker2_validate -0.108865843366939 2.38156077931383e-27 NA NA NA hsa-miR-21-5p GLCCI1 1.0504925175311 2.58081295984106e-11 -0.0823006336730128 0.352914294038513 miRNAWalker2_validate -0.217874607401214 2.41448912330539e-18 NA NA NA hsa-miR-21-5p GPAM 1.0504925175311 2.58081295984106e-11 -0.341005823569965 4.88915423999009e-07 miRNAWalker2_validate -0.136627940890528 1.67993460974671e-13 NA NA NA hsa-miR-21-5p GPD1L 1.0504925175311 2.58081295984106e-11 -0.282460523791179 5.21672204438394e-05 miRNAWalker2_validate -0.132638887067449 1.19836045418045e-11 NA NA NA hsa-miR-21-5p HAPLN1 1.0504925175311 2.58081295984106e-11 -0.791996101418164 1.20626116359587e-05 miRNAWalker2_validate -0.57501061406315 1.42672109182052e-26 NA NA NA hsa-miR-21-5p HMGB3 1.0504925175311 2.58081295984106e-11 0.110904170774731 0.0931861531179716 miRNAWalker2_validate -0.121927776772609 9.10050740075751e-12 NA NA NA hsa-miR-10b-5p IGSF1 1.54586540986745 2.64595843546465e-08 -0.9397340491218 3.97973216458896e-08 miRNAWalker2_validate -0.123204439431774 4.70746336114285e-06 NA NA NA hsa-miR-10b-5p IPCEF1 1.54586540986745 2.64595843546465e-08 -0.637962579640793 2.88980073139746e-06 miRNAWalker2_validate -0.109802235839446 2.92283312596912e-07 NA NA NA hsa-miR-21-5p JMY 1.0504925175311 2.58081295984106e-11 -0.187444686363918 0.000120412578133134 miRNAWalker2_validate -0.11042748697577 7.06004584727729e-23 NA NA NA hsa-miR-21-5p JPH1 1.0504925175311 2.58081295984106e-11 -0.319996540716788 0.0305372995080731 miRNAWalker2_validate -0.112985525859259 0.0149441630081063 NA NA NA hsa-miR-21-5p KBTBD6 1.0504925175311 2.58081295984106e-11 -0.237145657072579 3.83297854058141e-05 miRNAWalker2_validate -0.178328468398766 1.92097037483054e-37 NA NA NA hsa-miR-21-5p KBTBD7 1.0504925175311 2.58081295984106e-11 -0.289087246425916 0.000559435751981594 miRNAWalker2_validate -0.20239814928466 3.73098236062684e-16 NA NA NA hsa-miR-21-5p LIFR 1.0504925175311 2.58081295984106e-11 -0.385582205083604 2.53026450447379e-05 miRNAWalker2_validate -0.132291774046052 1.09714642870804e-07 NA NA NA hsa-miR-21-5p LONRF2 1.0504925175311 2.58081295984106e-11 -0.336492098006701 0.000122708148335347 miRNAWalker2_validate -0.189870255774996 8.90045612819168e-15 NA NA NA hsa-miR-21-5p LYRM7 1.0504925175311 2.58081295984106e-11 -0.115166815412413 0.0180822614500249 miRNAWalker2_validate -0.125819502010951 4.41161135165989e-28 NA NA NA hsa-miR-21-5p MARCKS 1.0504925175311 2.58081295984106e-11 -0.105877798606951 0.190059303769791 miRNAWalker2_validate;miRTarBase -0.143908434517577 3.43031120392992e-14 19302977 MicroRNA 21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells drug resistance prostate cancer hsa-miR-21-5p MIB1 1.0504925175311 2.58081295984106e-11 -0.197304309194696 0.00153060773556678 miRNAWalker2_validate -0.116776532207112 1.86852217406626e-14 NA NA NA hsa-miR-21-5p MOAP1 1.0504925175311 2.58081295984106e-11 -0.368003334728375 1.41047632768789e-07 miRNAWalker2_validate -0.205987474173013 2.22771555814876e-30 NA NA NA hsa-miR-21-5p MRAP2 1.0504925175311 2.58081295984106e-11 -0.127101744201301 0.494782817103401 miRNAWalker2_validate -0.181066948791156 0.00190689564121909 NA NA NA hsa-miR-21-5p MTMR9 1.0504925175311 2.58081295984106e-11 -0.205234916118923 0.000122593622990093 miRNAWalker2_validate -0.134241274773015 9.82011394770466e-25 NA NA NA hsa-miR-21-5p MYCBP2 1.0504925175311 2.58081295984106e-11 -0.354075360345454 2.76928595468988e-06 miRNAWalker2_validate -0.161032250080632 4.70297695422002e-15 NA NA NA hsa-miR-21-5p NBEA 1.0504925175311 2.58081295984106e-11 -0.365452323213813 1.42551340934486e-05 miRNAWalker2_validate -0.241805042283778 5.15469149787601e-24 NA NA NA hsa-miR-21-5p NFIB 1.0504925175311 2.58081295984106e-11 -0.151336169908416 0.0298860513853996 miRNAWalker2_validate;miRTarBase -0.142102552193434 7.18924216890823e-16 NA NA NA hsa-miR-21-5p PER3 1.0504925175311 2.58081295984106e-11 -0.555621926560449 4.66702527917726e-11 miRNAWalker2_validate -0.159315752042598 5.9947352989701e-11 NA NA NA hsa-miR-21-5p PIK3R1 1.0504925175311 2.58081295984106e-11 -0.259275224308753 0.00106935451973482 miRNAWalker2_validate -0.192193122796698 2.35557430088274e-23 26676464 PIK3R1 targeting by miR 21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT and predicts clinical outcome of breast cancer; Next we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21; Taken together we provide novel evidence that miR-21 knockdown suppresses cell growth migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer cell migration breast cancer hsa-miR-21-5p PPARA 1.0504925175311 2.58081295984106e-11 -0.335389759038048 2.96327925125206e-07 miRNAWalker2_validate;miRTarBase -0.11018993610431 8.20918004042089e-10 22244963 In the final integrative analysis of lung cancer related miR-21-targets analysis 24 hub genes were identified by overlap calculation suggesting that miR-21 may play an important role in the development and progression of lung cancer through JAK/STAT signal pathway MAPK signaling pathway Wnt signaling pathway cell cycle PPAR signaling pathway apoptosis pathway and other pathways progression lung cancer hsa-miR-21-5p PPFIA4 1.0504925175311 2.58081295984106e-11 -0.314552060489406 0.00327681375564529 miRNAWalker2_validate -0.214316382147153 4.36650074034371e-11 NA NA NA hsa-miR-21-5p PPIF 1.0504925175311 2.58081295984106e-11 -0.144644009312107 0.0748430302545273 miRNAWalker2_validate -0.101588005740477 3.5783040278114e-06 NA NA NA hsa-miR-21-5p PPM1L 1.0504925175311 2.58081295984106e-11 -0.486425204824598 5.55955313078931e-06 miRNAWalker2_validate -0.204711891718498 3.74665604938713e-10 NA NA NA hsa-miR-21-5p PRKCE 1.0504925175311 2.58081295984106e-11 -0.435078897352525 2.43836196620233e-06 miRNAWalker2_validate -0.251627359565709 1.17020373706199e-21 NA NA NA hsa-miR-21-5p PTGFR 1.0504925175311 2.58081295984106e-11 -0.540035302564516 0.000975822554466034 miRNAWalker2_validate -0.276530616548992 5.58349391099745e-08 NA NA NA hsa-miR-10b-5p PTPRT 1.54586540986745 2.64595843546465e-08 -1.26869586166531 7.57841447656641e-15 miRNAWalker2_validate -0.180921784406605 1.11245437106782e-12 NA NA NA hsa-miR-21-5p RAB11FIP2 1.0504925175311 2.58081295984106e-11 -0.291509608716314 5.28928624638561e-07 miRNAWalker2_validate -0.136949981828519 3.29047375180848e-18 NA NA NA hsa-miR-21-5p RASGRP1 1.0504925175311 2.58081295984106e-11 -0.461228311355649 9.75402712538101e-05 miRNAWalker2_validate;miRTarBase -0.209857300737546 6.88556700859861e-09 NA NA NA hsa-miR-21-5p RUFY3 1.0504925175311 2.58081295984106e-11 -0.261130523548589 3.72002658101746e-05 miRNAWalker2_validate -0.116067020001459 2.3024733997506e-17 NA NA NA hsa-miR-21-5p SAMD5 1.0504925175311 2.58081295984106e-11 -0.312026167088983 0.00676160573456063 miRNAWalker2_validate -0.18283676771492 3.42276539091039e-07 NA NA NA hsa-miR-21-5p SASH1 1.0504925175311 2.58081295984106e-11 -0.343138665104062 2.88016197509997e-06 miRNAWalker2_validate -0.163897485534976 2.74923434805187e-16 NA NA NA hsa-miR-21-5p SERPINI1 1.0504925175311 2.58081295984106e-11 -0.811105258131413 9.01706463193578e-09 miRNAWalker2_validate -0.287112829992799 6.87011471922936e-11 22464652 MicroRNA 21 inhibits Serpini1 a gene with novel tumour suppressive effects in gastric cancer; Molecular techniques include microRNA microarrays cDNA microarrays qRT-PCR for miR and mRNA expression transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting cell cycle analysis by flow cytometry and luciferase reporter assay; This search identified Serpini1 as a putative miR-21 target; Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers suggesting a regulatory mechanism that included both of these molecules; Taken together these data suggest that in a subgroup of gastric cancers miR-21 is upregulated inducing downregulation of Serpini1 which in turn releases the G1-S transition checkpoint with the end result being increased tumour growth gastric cancer hsa-miR-21-5p SFXN1 1.0504925175311 2.58081295984106e-11 -0.110169374321768 0.0288458211648728 miRNAWalker2_validate -0.108789407938724 8.3128022603272e-23 NA NA NA hsa-miR-21-5p SLC9A6 1.0504925175311 2.58081295984106e-11 -0.356244449389569 6.6188187319312e-09 miRNAWalker2_validate -0.166026417528454 5.4048929917626e-27 NA NA NA hsa-miR-21-5p SMAD7 1.0504925175311 2.58081295984106e-11 -0.306923934978072 7.06110046856494e-08 miRNAWalker2_validate -0.126701222262503 3.62596651934364e-16 23372687;27185036;26531758 Furthermore the expression of MSH2 and SMAD7 two important molecules involving TGF-β pathway was restored following miR-21 knockdown in both MCF-7 and Hs578T breast cancer cells;MicroRNA 21 Regulates Non Small Cell Lung Cancer Cell Invasion and Chemo Sensitivity through SMAD7; We performed bioinformatics analyses on the binding of microRNA-21 miR-21 to the 3'-UTR of SMAD7 mRNA and verified the biological effects of this binding using promoter luciferase reporter assay; Furthermore expression of miR-21 was found to be inhibited by Carboplatin and bioinformatics analyses showed that miR-21 targeted the 3'-UTR of SMAD7 mRNA to inhibit its translation which was confirmed by luciferase reporter assay; Carboplatin may upregulate SMAD7 through suppression of miR-21 to inhibit TGFβ receptor signaling mediated NSCLC cell invasion;MicroRNA 21 induces breast cancer cell invasion and migration by suppressing smad7 via EGF and TGF β pathways; The present study was undertaken to determine the association of miR-21 smad7 EGF and TGF-β with breast cancer cell invasion and migration and to identify the molecular mechanisms involved using immunohistochemistry and western blot analysis; Smad7 was confirmed to be a direct target of miR-21 by luciferase reporter and western blot assays; The downregulation of smad7 by miR-21 or sismad7 enhanced EGF-dependent invasion and migration as well as TGF-β-dependent invasion and migration; The actions of miR-21 were abrogated by expressing a modified smad7 cDNA resistant to miR-21; In conclusion our results demonstrated that plasma miR-21 levels may serve as a diagnostic marker in breast cancers whereas miR-21 promotes breast cancer cell proliferation and invasion by suppressing smad7 which enhances EGF and TGF-β pathways ;; breast cancer;lung squamous cell cancer;breast cancer hsa-miR-21-5p STXBP5 1.0504925175311 2.58081295984106e-11 -0.332112784351769 0.00028702296326662 miRNAWalker2_validate -0.209748977000397 4.38001613145774e-14 NA NA NA hsa-miR-21-5p TET1 1.0504925175311 2.58081295984106e-11 -0.32640694280031 0.000352680131894529 miRNAWalker2_validate -0.277255774566943 8.28651614470572e-25 NA NA NA hsa-miR-21-5p TMEM56 1.0504925175311 2.58081295984106e-11 -0.734448370607854 2.87117277016386e-10 miRNAWalker2_validate -0.18827883198366 1.99967651992057e-07 NA NA NA hsa-miR-21-5p TNRC6B 1.0504925175311 2.58081295984106e-11 -0.14264032553339 0.00666673288900001 miRNAWalker2_validate -0.106085793450043 3.49481999435528e-18 NA NA NA hsa-miR-21-5p TRAPPC2 1.0504925175311 2.58081295984106e-11 -0.116359119411045 0.0101735884502882 miRNAWalker2_validate -0.107205543511503 4.42861150925895e-19 NA NA NA hsa-miR-21-5p TRIM2 1.0504925175311 2.58081295984106e-11 -0.33677573869651 5.35148232030248e-07 miRNAWalker2_validate -0.13223015871936 3.6594114148697e-15 NA NA NA hsa-miR-21-5p TTC33 1.0504925175311 2.58081295984106e-11 -0.232700603279568 3.77213850680935e-06 miRNAWalker2_validate -0.125357110780225 5.0654558881752e-23 NA NA NA hsa-miR-21-5p VASH2 1.0504925175311 2.58081295984106e-11 0.281394374703269 0.0109642635707859 miRNAWalker2_validate -0.193246837470003 1.84139602950109e-08 NA NA NA hsa-miR-21-5p ZADH2 1.0504925175311 2.58081295984106e-11 -0.192673735140135 6.56665105974276e-05 miRNAWalker2_validate -0.109341729294079 3.01472985607581e-21 NA NA NA hsa-miR-21-5p ZBTB20 1.0504925175311 2.58081295984106e-11 -0.0704517263025557 0.518912297577961 miRNAWalker2_validate -0.1136165215619 0.000842493213345978 NA NA NA hsa-miR-21-5p ZBTB47 1.0504925175311 2.58081295984106e-11 -0.326204469427715 5.38041835296573e-07 miRNAWalker2_validate -0.164188112509787 3.13994421531149e-25 NA NA NA hsa-miR-21-5p ZNF292 1.0504925175311 2.58081295984106e-11 -0.103944442236856 0.0965225647483346 miRNAWalker2_validate -0.116488277623481 4.68413699651989e-13 NA NA NA hsa-miR-21-5p ZRANB1 1.0504925175311 2.58081295984106e-11 -0.330689908425904 8.62610610532771e-10 miRNAWalker2_validate -0.154217873636795 1.22817464045126e-34 NA NA NA