Explanation
This regulatory network was inferred from the input dataset. The miRNAs and mRNAs are
presented as round and rectangle nodes respectively. The numerical value popped up upon mouse over the gene node is the log2 transformed fold-change of the gene expression between the two groups. All of the nodes are clickable, and the detailed information of the miRNAs/mRNAs and related cancer pathway will be displayed in another window. The edges between nodes are supported by both interactions (predicted or experimentally verified) and correlations learnt from cancer dataset. The numerical value popped up upon mouse over the edge is the correlation beat value (effect size) between the two nodes. The experimental evidences of the edges reported in previous cancer studies are highlighted by red/orange color. All of these information can be accessed by the "mouse-over" action. This network shows a full map of the miRNA-mRNA regulation of the input gene list(s), and the hub miRNAs (with the high network degree/betweenness centrality) would be the potential cancer drivers or tumor suppressors. The full result table can be accessed in the "Regulations" tab.
"miRNACancerMAP" is also a network visualization tool for users to draw their regulatory network by personal customization. Users can set the complexity of the network by limiting the number of nodes or edges. And the color of the nodes can be defined by different categories of the mRNAs and miRNAs, such as Gene-Ontology, pathway, and expression status. Users can also select to use network degree or network betweenness centrality to define the node size. And edges can be black or colored by the correlation. Purple edge means negative correlation (mostly found between miRNA and mRNA), and blue edge means positive correlation (found in PPI or miRNA-miRNA sponge effect). We can also add the protein-protein interactions (PPI) into the network. This result will show the cluster of genes regulated by some specific miRNAs. Additionally, miRNA-miRNA edges can be added by the "miRNA sponge" button, presenting some clusters of miRNAs that have the interactions via sponge effect.
miRNA-gene regulations
| Num | microRNA | Gene | miRNA log2FC | miRNA pvalue | Gene log2FC | Gene pvalue | Interaction | Correlation beta | Correlation P-value | PMID | Reported in cancer studies |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | hsa-miR-183-5p | ABCA1 | -1.22 | 0 | 1.48 | 0 | MirTarget; miRNATAP | -0.11 | 0.00192 | 26935154 | MiR 183 functions as an oncogene by targeting ABCA1 in colon cancer; We found that miR-183 targets the 3'UTR of ABCA1 mRNA; Subsequent experiments confirmed that miR-183 degraded ABCA1 mRNA in the colon cancer cells; Thus we conclude that miR-183 promotes proliferation and inhibits apoptosis by degrading ABCA1 in colon cancer |
| 2 | hsa-miR-183-5p | AJAP1 | -1.22 | 0 | -1.5 | 0 | MirTarget | -0.13 | 0.01583 | NA | |
| 3 | hsa-miR-183-5p | ARHGAP26 | -1.22 | 0 | 1.01 | 0 | MirTarget | -0.17 | 0 | NA | |
| 4 | hsa-miR-183-5p | ARHGAP32 | -1.22 | 0 | 0.03 | 0.68296 | miRNAWalker2 validate | -0.14 | 0 | NA | |
| 5 | hsa-miR-183-5p | BCL11B | -1.22 | 0 | 1.57 | 0 | miRNAWalker2 validate; miRNATAP | -0.14 | 0.00111 | NA | |
| 6 | hsa-miR-183-5p | BNIP3L | -1.22 | 0 | 0.88 | 0 | MirTarget; miRNATAP | -0.11 | 0 | NA | |
| 7 | hsa-miR-183-5p | CACNA1E | -1.22 | 0 | 0.4 | 0.06883 | miRNATAP | -0.13 | 0.01941 | NA | |
| 8 | hsa-miR-183-5p | CCDC85C | -1.22 | 0 | -0.39 | 6.0E-5 | mirMAP | -0.13 | 0 | NA | |
| 9 | hsa-miR-183-5p | CCND1 | -1.22 | 0 | 2.13 | 0 | miRNAWalker2 validate | -0.37 | 0 | NA | |
| 10 | hsa-miR-183-5p | CELF6 | -1.22 | 0 | 0.75 | 8.0E-5 | MirTarget | -0.15 | 0.00154 | NA | |
| 11 | hsa-miR-183-5p | CLCN6 | -1.22 | 0 | 0.18 | 0.0226 | mirMAP | -0.14 | 0 | NA | |
| 12 | hsa-miR-183-5p | CTDSP1 | -1.22 | 0 | 0.29 | 3.0E-5 | miRNATAP | -0.12 | 0 | NA | |
| 13 | hsa-miR-183-5p | CX3CL1 | -1.22 | 0 | 0.95 | 0 | MirTarget | -0.23 | 0 | NA | |
| 14 | hsa-miR-183-5p | CYYR1 | -1.22 | 0 | 0.26 | 0.0413 | MirTarget | -0.21 | 0 | NA | |
| 15 | hsa-miR-183-5p | DGKE | -1.22 | 0 | -0.21 | 0.04996 | miRNATAP | -0.15 | 0 | NA | |
| 16 | hsa-miR-183-5p | EMP2 | -1.22 | 0 | 0.12 | 0.24234 | MirTarget | -0.12 | 0 | NA | |
| 17 | hsa-miR-183-5p | EPHA4 | -1.22 | 0 | -0.75 | 0 | miRNATAP | -0.23 | 0 | NA | |
| 18 | hsa-miR-183-5p | EZR | -1.22 | 0 | 0.23 | 0.00918 | miRNAWalker2 validate; miRTarBase; MirTarget; miRNATAP | -0.13 | 0 | 24352761; 22525461; 22851079; 21176563; 25337200; 22922800; 18840437; 20858276 | MicroRNA-183 miR-183 has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin; The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas; Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas; MiR-183 and Ezrin mRNA expression levels were respectively lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly both P < 0.001; Notably the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues r = -0.66 P = 0.01; In addition the combined miR-183 downregulation and Ezrin upregulation miR-183-low/Ezrin-high was significantly associated with high tumor grade P = 0.02 poor response to chemotherapy P = 0.01 positive metastasis P = 0.006 and recurrence P = 0.008; Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma;Down regulation of miR 183 promotes migration and invasion of osteosarcoma by targeting Ezrin; Using a luciferase reporter carrying the 3'-untranslated region 3'-UTR of Ezrin we identified Ezrin as a direct target of miR-183; Of interest suppression of Ezrin by miR-183 caused a reduction of phosphorylated p44/42 p-p44/42; Finally suppression of Ezrin by RNAi mimicked miR-183 action in the suppression of migration and invasion which was associated with down-regulation of p-p44/42;Expression of microRNA 183 in stage II gastric cancer and its association with Ezrin protein; To investigate the expression of microRNA-183 miR-183 and Ezrin protein in stage II gastric cancer GC; The associations of miR-183 expression with the clinicopathologic features of stage II GC and Ezrin expression were analyzed; Ezrin is a potential regulatory protein of miR-183;2 By a functional screen using miRNA microarray combined with bioinformatics analysis the miR-183 and miR-22 were indentified as two candidate miRNA which may have the potential regulatory role in ezrin expression; A subsequent validation by western blot and real time RT-PCR revealed that over-expression of miR-183 and miR-22 could both lead to an obvious decrease in ezrin protein level while there were not signicant difference in the level of ezrin mRNA P > 0.05;miR 183 inhibits invasion of gastric cancer by targeting Ezrin; Overexpression of miR-183 markedly suppressed cells invasion by downregulation of Ezrin expression; In conclusion our study demonstrated that miR-183 acts as a tumor suppressor in GC partially at least via regulation of Ezrin;miR 183 inhibits the metastasis of osteosarcoma via downregulation of the expression of Ezrin in F5M2 cells; In our study ectopic overexpression of miR-183 repressed the expression levels of Ezrin and significantly inhibited the motility and invasion of osteosarcoma cells; This suggests that miR-183 may possibly play a tumor suppressor role in the metastasis of osteosarcoma by downregulating Ezrin expression levels; These findings show that through inhibition of Ezrin expression levels miR-183 is significantly involved in cell migration and invasion of osteosarcoma;MicroRNA 183 regulates Ezrin expression in lung cancer cells; Mechanistically we identified VIL2-coding-protein Ezrin as a bona fide target of miR-183;Specifically the VIL2-coding protein Ezrin was confirmed as a target of miR-183 and downregulation of this protein was confirmed with immunocytochemistry; These findings indicate that miR-183 targets VIL2 and may play a central role in the regulation of migration and metastasis in breast cancer |
| 19 | hsa-miR-183-5p | FRMD6 | -1.22 | 0 | 0.2 | 0.06292 | MirTarget; miRNATAP | -0.11 | 0.00013 | NA | |
| 20 | hsa-miR-183-5p | GYPA | -1.22 | 0 | -0.87 | 0.01279 | MirTarget | -0.38 | 1.0E-5 | NA | |
| 21 | hsa-miR-183-5p | HLA-A | -1.22 | 0 | 1.72 | 0 | miRNAWalker2 validate | -0.11 | 0.001 | NA | |
| 22 | hsa-miR-183-5p | ITGA5 | -1.22 | 0 | 2.04 | 0 | miRNAWalker2 validate | -0.17 | 4.0E-5 | NA | |
| 23 | hsa-miR-183-5p | ITGA8 | -1.22 | 0 | -1.18 | 0 | miRNAWalker2 validate | -0.13 | 0.04115 | NA | |
| 24 | hsa-miR-183-5p | JAM3 | -1.22 | 0 | 0.41 | 0.00016 | MirTarget | -0.2 | 0 | NA | |
| 25 | hsa-miR-183-5p | KCNMA1 | -1.22 | 0 | 2.38 | 0 | miRNATAP | -0.32 | 0 | NA | |
| 26 | hsa-miR-183-5p | KDELC2 | -1.22 | 0 | 0.71 | 0 | miRNAWalker2 validate | -0.13 | 0 | NA | |
| 27 | hsa-miR-183-5p | KIAA0355 | -1.22 | 0 | 0.04 | 0.53434 | MirTarget; miRNATAP | -0.12 | 0 | NA | |
| 28 | hsa-miR-183-5p | KIAA1614 | -1.22 | 0 | -0.08 | 0.49276 | mirMAP | -0.15 | 0 | NA | |
| 29 | hsa-miR-183-5p | KIF21B | -1.22 | 0 | 2.44 | 0 | mirMAP | -0.2 | 4.0E-5 | NA | |
| 30 | hsa-miR-183-5p | KIF5C | -1.22 | 0 | -0.71 | 0 | miRNAWalker2 validate; MirTarget | -0.12 | 0.00131 | NA | |
| 31 | hsa-miR-183-5p | KLHL23 | -1.22 | 0 | 0.17 | 0.23069 | miRNAWalker2 validate; MirTarget | -0.17 | 0 | NA | |
| 32 | hsa-miR-183-5p | KLRD1 | -1.22 | 0 | 2.74 | 0 | MirTarget | -0.23 | 1.0E-5 | NA | |
| 33 | hsa-miR-183-5p | LENG8 | -1.22 | 0 | 1.08 | 0 | miRNAWalker2 validate | -0.11 | 0.00506 | NA | |
| 34 | hsa-miR-183-5p | MAP3K13 | -1.22 | 0 | 0.21 | 0.1373 | MirTarget; miRNATAP | -0.1 | 0.00459 | NA | |
| 35 | hsa-miR-183-5p | MEF2C | -1.22 | 0 | 1.19 | 0 | MirTarget; miRNATAP | -0.21 | 0 | NA | |
| 36 | hsa-miR-183-5p | MICA | -1.22 | 0 | 0.45 | 0 | MirTarget | -0.11 | 0 | NA | |
| 37 | hsa-miR-183-5p | NCK2 | -1.22 | 0 | 0.74 | 0 | MirTarget; miRNATAP | -0.1 | 0 | NA | |
| 38 | hsa-miR-183-5p | NHSL2 | -1.22 | 0 | -0.27 | 0.09311 | miRNAWalker2 validate | -0.1 | 0.01206 | NA | |
| 39 | hsa-miR-183-5p | NOVA2 | -1.22 | 0 | 1.75 | 0 | mirMAP | -0.35 | 0 | NA | |
| 40 | hsa-miR-183-5p | NRG1 | -1.22 | 0 | -0.51 | 0.00483 | miRNATAP | -0.13 | 0.00606 | NA | |
| 41 | hsa-miR-183-5p | NRIP2 | -1.22 | 0 | 0.34 | 0.01097 | MirTarget | -0.19 | 0 | NA | |
| 42 | hsa-miR-183-5p | NRP2 | -1.22 | 0 | 1.96 | 0 | miRNATAP | -0.19 | 0 | NA | |
| 43 | hsa-miR-183-5p | NRXN3 | -1.22 | 0 | 0.86 | 0 | miRNATAP | -0.13 | 0.00435 | NA | |
| 44 | hsa-miR-183-5p | PAQR9 | -1.22 | 0 | 2.89 | 0 | MirTarget | -0.15 | 0.04789 | NA | |
| 45 | hsa-miR-183-5p | PCDH19 | -1.22 | 0 | -0.81 | 0 | mirMAP | -0.11 | 0.00624 | NA | |
| 46 | hsa-miR-183-5p | PLCH2 | -1.22 | 0 | -0.01 | 0.96965 | mirMAP | -0.29 | 1.0E-5 | NA | |
| 47 | hsa-miR-183-5p | PLD1 | -1.22 | 0 | 0.46 | 1.0E-5 | mirMAP | -0.18 | 0 | NA | |
| 48 | hsa-miR-183-5p | PPM1F | -1.22 | 0 | 0.99 | 0 | mirMAP | -0.22 | 0 | NA | |
| 49 | hsa-miR-183-5p | PRUNE2 | -1.22 | 0 | 1.05 | 0 | miRNATAP | -0.3 | 0 | NA | |
| 50 | hsa-miR-183-5p | RALGDS | -1.22 | 0 | 1.1 | 0 | miRNAWalker2 validate; MirTarget; miRNATAP | -0.18 | 0 | NA | |
| 51 | hsa-miR-183-5p | RHOB | -1.22 | 0 | 0.71 | 0 | miRNATAP | -0.28 | 0 | NA | |
| 52 | hsa-miR-183-5p | RHOBTB1 | -1.22 | 0 | 1.07 | 0 | miRNATAP | -0.15 | 6.0E-5 | NA | |
| 53 | hsa-miR-183-5p | RORA | -1.22 | 0 | 0.33 | 0.00063 | miRNATAP | -0.13 | 0 | NA | |
| 54 | hsa-miR-183-5p | RUNX1T1 | -1.22 | 0 | -0.64 | 0.00048 | miRNATAP | -0.18 | 9.0E-5 | NA | |
| 55 | hsa-miR-183-5p | SACS | -1.22 | 0 | 1.32 | 0 | MirTarget; miRNATAP | -0.12 | 0.0001 | NA | |
| 56 | hsa-miR-183-5p | SH3BP2 | -1.22 | 0 | 1.63 | 0 | mirMAP | -0.21 | 0 | NA | |
| 57 | hsa-miR-183-5p | SLC2A3 | -1.22 | 0 | 2.08 | 0 | miRNAWalker2 validate | -0.24 | 0 | NA | |
| 58 | hsa-miR-183-5p | SPC25 | -1.22 | 0 | 2.7 | 0 | MirTarget | -0.12 | 0.04813 | NA | |
| 59 | hsa-miR-183-5p | SPN | -1.22 | 0 | 2.31 | 0 | mirMAP | -0.2 | 4.0E-5 | NA | |
| 60 | hsa-miR-183-5p | SPRED1 | -1.22 | 0 | 0.57 | 0 | miRNATAP | -0.12 | 0 | NA | |
| 61 | hsa-miR-183-5p | ST6GALNAC3 | -1.22 | 0 | -1.18 | 0 | MirTarget | -0.17 | 4.0E-5 | NA | |
| 62 | hsa-miR-183-5p | STC1 | -1.22 | 0 | 0.14 | 0.38635 | miRNATAP | -0.13 | 0.00136 | NA | |
| 63 | hsa-miR-183-5p | STX1B | -1.22 | 0 | 1.53 | 0 | mirMAP | -0.25 | 0 | NA | |
| 64 | hsa-miR-183-5p | TCF4 | -1.22 | 0 | 1 | 0 | miRNATAP | -0.23 | 0 | NA | |
| 65 | hsa-miR-183-5p | THRA | -1.22 | 0 | -0.67 | 0 | mirMAP | -0.1 | 0 | NA | |
| 66 | hsa-miR-183-5p | THSD7B | -1.22 | 0 | -0.82 | 0.00023 | miRNATAP | -0.19 | 0.00059 | NA | |
| 67 | hsa-miR-183-5p | TMCC3 | -1.22 | 0 | 0.38 | 0.0005 | MirTarget; miRNATAP | -0.22 | 0 | NA | |
| 68 | hsa-miR-183-5p | TRPC6 | -1.22 | 0 | 0.42 | 0.00937 | MirTarget | -0.18 | 1.0E-5 | NA | |
| 69 | hsa-miR-183-5p | TUB | -1.22 | 0 | -1.16 | 0 | MirTarget | -0.14 | 0.01202 | NA | |
| 70 | hsa-miR-183-5p | VASH1 | -1.22 | 0 | 2.22 | 0 | mirMAP | -0.23 | 0 | NA | |
| 71 | hsa-miR-183-5p | WDFY4 | -1.22 | 0 | 2.22 | 0 | mirMAP | -0.11 | 0.04576 | NA | |
| 72 | hsa-miR-183-5p | ZEB1 | -1.22 | 0 | 0.52 | 0 | MirTarget; miRNATAP | -0.2 | 0 | NA | |
| 73 | hsa-miR-183-5p | ZFPM2 | -1.22 | 0 | 0.23 | 0.12521 | miRNATAP | -0.18 | 0 | NA | |
| 74 | hsa-miR-183-5p | ZNF154 | -1.22 | 0 | 0.01 | 0.94371 | mirMAP | -0.16 | 1.0E-5 | NA | |
| 75 | hsa-miR-183-5p | ZNF395 | -1.22 | 0 | 2.37 | 0 | mirMAP | -0.36 | 0 | NA |
| Num | GO | Overlap | Size | P Value | Adj. P Value |
|---|---|---|---|---|---|
| 1 | BIOLOGICAL ADHESION | 17 | 1032 | 1.991e-07 | 0.0009263 |
| 2 | POSITIVE REGULATION OF MULTICELLULAR ORGANISMAL PROCESS | 18 | 1395 | 2.863e-06 | 0.00431 |
| 3 | LOCOMOTION | 16 | 1114 | 2.934e-06 | 0.00431 |
| 4 | MOVEMENT OF CELL OR SUBCELLULAR COMPONENT | 17 | 1275 | 3.705e-06 | 0.00431 |
| 5 | SINGLE ORGANISM CELL ADHESION | 10 | 459 | 8.03e-06 | 0.005635 |
| 6 | TAXIS | 10 | 464 | 8.825e-06 | 0.005635 |
| 7 | BLOOD VESSEL MORPHOGENESIS | 9 | 364 | 8.655e-06 | 0.005635 |
| 8 | VASCULATURE DEVELOPMENT | 10 | 469 | 9.689e-06 | 0.005635 |
| 9 | ANGIOGENESIS | 8 | 293 | 1.39e-05 | 0.007187 |
| 10 | CELL CELL ADHESION | 11 | 608 | 1.57e-05 | 0.007305 |
| 11 | CELL MORPHOGENESIS INVOLVED IN DIFFERENTIATION | 10 | 513 | 2.1e-05 | 0.008884 |
| Num | GO | Overlap | Size | P Value | Adj. P Value |
|---|---|---|---|---|---|
| 1 | PROTEIN COMPLEX BINDING | 14 | 935 | 8.449e-06 | 0.007849 |
| Num | GO | Overlap | Size | P Value | Adj. P Value |
|---|---|---|---|---|---|
| 1 | APICAL PART OF CELL | 9 | 361 | 8.099e-06 | 0.00473 |
| 2 | CELL SURFACE | 12 | 757 | 2.317e-05 | 0.006766 |
Over-represented Pathway
| Num | Pathway | Pathview | Overlap | Size | P Value | Adj. P Value |
|---|---|---|---|---|---|---|
| 1 | Cell_adhesion_molecules_.CAMs._hsa04514 | 5 | 145 | 0.0002146 | 0.01116 | |
| 2 | Phospholipase_D_signaling_pathway_hsa04072 | 3 | 146 | 0.01755 | 0.282 | |
| 3 | cGMP_PKG_signaling_pathway_hsa04022 | 3 | 163 | 0.0234 | 0.282 | |
| 4 | Tight_junction_hsa04530 | 3 | 170 | 0.02608 | 0.282 | |
| 5 | ECM_receptor_interaction_hsa04512 | 2 | 82 | 0.038 | 0.282 | |
| 6 | Focal_adhesion_hsa04510 | 3 | 199 | 0.03887 | 0.282 | |
| 7 | ErbB_signaling_pathway_hsa04012 | 2 | 85 | 0.04056 | 0.282 | |
| 8 | Regulation_of_actin_cytoskeleton_hsa04810 | 3 | 208 | 0.04338 | 0.282 | |
| 9 | Endocytosis_hsa04144 | 3 | 244 | 0.06389 | 0.3691 | |
| 10 | Apelin_signaling_pathway_hsa04371 | 2 | 137 | 0.0936 | 0.4199 | |
| 11 | MAPK_signaling_pathway_hsa04010 | 3 | 295 | 0.09915 | 0.4199 | |
| 12 | Phagosome_hsa04145 | 2 | 152 | 0.1113 | 0.4199 | |
| 13 | Hippo_signaling_pathway_hsa04390 | 2 | 154 | 0.1138 | 0.4199 | |
| 14 | Cellular_senescence_hsa04218 | 2 | 160 | 0.1211 | 0.4199 | |
| 15 | PI3K_Akt_signaling_pathway_hsa04151 | 3 | 352 | 0.1458 | 0.4681 | |
| 16 | Ras_signaling_pathway_hsa04014 | 2 | 232 | 0.2162 | 0.5591 |
