Background
Methods
Primary mouse hepatocyte isolation and culture
Cell viability assay
Microarray experiment and quantitative real-time polymerase chain reaction
Microarray data analysis
Temporal expression of genes and microRNAs
Integration of mRNA and microRNA expression
Pathway enrichment
Pathway activity
Core microRNA targets from multiple pathways
Transcription factors binding sites analysis
Results
Temporal pattern of genes and microRNA expression
Integration of gene and microRNA expression
Temporal up-pattern | ||||||||
---|---|---|---|---|---|---|---|---|
MicroRNA* | Target symbol | Target entrez | MicroRNA | Target symbol | Target entrez | MicroRNA | Target symbol | Target entrez |
miR-495-3p | Depdc1b | 218581 | miR-19b-2-5p | Sprr2a2 | 1E + 08 | miR-3089-3p | Scara3 | 219151 |
Slc1a2 | 20511 | Mbnl3 | 171170 | Rad51 | 19361 | |||
Steap2 | 74051 | Cep55 | 74107 | miR-3095-5p | Gsta3 | 14859 | ||
Zmat1 | 215693 | Tia1 | 21841 | Ccnd1 | 12443 | |||
Fmo5 | 14263 | miR-3092-5p | Cln6 | 76524 | miR-30c-5p | Fam43a | 224093 | |
Ckap4 | 216197 | Lass3 | 545975 | Fam49a | 76820 | |||
Bcl2l15 | 229672 | Gsto1 | 14873 | miR-322-3p | Ugdh | 22235 | ||
Bst1 | 12182 | C1qtnf1 | 56745 | Mybl1 | 17864 | |||
Pttg1 | 30939 | miR-450a-2-3p | Slc7a2 | 11988 | miR-343 | Mybl2 | 17865 | |
Osbpl3 | 71720 | Slc1a2 | 20511 | Nfasc | 269116 | |||
Esco2 | 71988 | Steap2 | 74051 | miR-380-5p | Cdon | 57810 | ||
4930547N16Rik | 75317 | Dcdc2a | 195208 | Ccdc89 | 70054 | |||
miR-669d-3p | Cenpi | 102920 | miR-466 k | Zscan29 | 99334 | miR-410-3p | Pla2r1 | 18779 |
Cysltr1 | 58861 | Dcdc2a | 195208 | Sema3e | 20349 | |||
Gnai1 | 14677 | Ptchd1 | 211612 | miR-449a-5p | Gpr64 | 237175 | ||
Zmat1 | 215693 | Saa4 | 20211 | H6pd | 100198 | |||
Rgs4 | 19736 | miR-653-3p | Igf2bp1 | 140486 | miR-466n-3p | Mest | 17294 | |
Kif23 | 71819 | Nfasc | 269116 | Dcdc2a | 195208 | |||
Fam55c | 385658 | Ect2 | 13605 | miR-467 g | Cxcl5 | 20311 | ||
Birc5 | 11799 | Lox | 16948 | Dcdc2a | 195208 | |||
Aspm | 12316 | miR-669 h-3p | Snap25 | 20614 | miR-5113 | Gbp4 | 17472 | |
Bub1 | 12235 | Steap2 | 74051 | Slc7a2 | 11988 | |||
Oip5 | 70645 | Cysltr1 | 58861 | miR-670-3p | Evl | 14026 | ||
Ckap2 | 80986 | Rgs4 | 19736 | Bcl2l15 | 229672 | |||
miR-98-3p | Clspn | 269582 | miR-697 | Ckap4 | 216197 | miR-692 | Marcks | 17118 |
Zfpm2 | 22762 | Slc1a2 | 20511 | Dcdc2a | 195208 | |||
Nfasc | 269116 | Fzd8 | 14370 | miR-693-3p | Akr1c14 | 105387 | ||
Ect2 | 13605 | Klf15 | 66277 | Nfasc | 269116 | |||
Ccna2 | 12428 | miR-881-5p | Serpine1 | 18787 | miR-701-3p | 1700029I01Rik | 70005 | |
Rad51 | 19361 | Slc1a2 | 20511 | Dcdc2a | 195208 | |||
Dock11 | 75974 | Steap2 | 74051 | miR-758-3p | Tpx2 | 72119 | ||
miR-21-3p | Nuf2 | 66977 | Fmo5 | 14263 | Zfpm2 | 22762 | ||
Steap2 | 74051 | miR-9-5p | Fam132b | 227358 | miR-875-3p | Cxcl3 | 330122 | |
Zfpm2 | 22762 | Lhfp | 108927 | Ehf | 13661 | |||
Fgf13 | 14168 | Galnt3 | 14425 | miR-122-5p | Samd5 | 320825 | ||
Sema3e | 20349 | Sort1 | 20661 | miR-134-5p | H6pd | 100198 | ||
Top2a | 21973 | let-7f-2-3p | Gm13154 | 433804 | miR-182-3p | Lhfpl2 | 218454 | |
miR-30b-5p | Igf2bp1 | 140486 | Fam164a | 67306 | miR-188-5p | Rspo3 | 72780 | |
Slc1a2 | 20511 | Ypel1 | 106369 | miR-1892 | Slc7a2 | 11988 | ||
Cysltr1 | 58861 | miR-107-3p | Rttn | 246102 | miR-1897-5p | Marcks | 17118 | |
Gnai1 | 14677 | Zfpm2 | 22762 | miR-193-3p | Abcc4 | 239273 | ||
Lox | 16948 | Shcbp1 | 20419 | miR-193-5p | Tspyl3 | 241732 | ||
Nedd4l | 83814 | miR-124-5p | Klhl13 | 67455 | miR-1950 | Axl | 26362 | |
miR-30d-5p | Prr11 | 270906 | Steap2 | 74051 | miR-1953 | Steap2 | 74051 | |
Cysltr1 | 58861 | Cd24a | 12484 | miR-195-3p | Cebpd | 12609 | ||
Gnai1 | 14677 | miR-1947-3p | Prrx1 | 18933 | miR-200a-5p | Fgf13 | 14168 | |
Lox | 16948 | Slc1a2 | 20511 | miR-200b-3p | Lhfp | 108927 | ||
Rnf219 | 72486 | Steap2 | 74051 | miR-203-5p | Abcc4 | 239273 | ||
Nedd4l | 83814 | miR-200a-3p | Thbd | 21824 | miR-206-3p | Nedd9 | 18003 | |
miR-466a-5p | Prc1 | 233406 | Mbnl3 | 171170 | miR-214-3p | Slc7a2 | 11988 | |
Slc1a2 | 20511 | Lhfp | 108927 | miR-216b-3p | Akr1c14 | 105387 | ||
Steap2 | 74051 | miR-291b-3p | Rtn1 | 104001 | miR-25-5p | Zfp365 | 216049 | |
Fam55c | 385658 | Kif23 | 71819 | miR-298-3p | Ccdc89 | 70054 | ||
Fgf23 | 64654 | Kit | 16590 | miR-29c-3p | Pxdn | 69675 | ||
Amotl1 | 75723 | miR-29b-2-5p | Fam55c | 385658 | miR-3062-5p | Ccdc89 | 70054 | |
miR-466o-3p | Gtse1 | 29870 | Gnai1 | 14677 | miR-3063-5p | Pak3 | 18481 | |
Zmat1 | 215693 | Zmat1 | 215693 | miR-3064-5p | Fbln2 | 14115 | ||
Kif23 | 71819 | miR-466i-3p | Tnfaip2 | 21928 | miR-3075-3p | Wisp1 | 22402 | |
Aspm | 12316 | Slc7a2 | 11988 | miR-3085-3p | Abcc1 | 17250 | ||
Gpr64 | 237175 | Gbp4 | 17472 | miR-3094-5p | Fgf23 | 64654 | ||
Serpinb1b | 282663 | miR-669c-3p | Tnfaip2 | 21928 | miR-3103-3p | Scarf2 | 224024 | |
miR-669 l-3p | Bmf | 171543 | Slc7a2 | 11988 | miR-3112-5p | Ptchd1 | 211612 | |
Fzd8 | 14370 | Adm | 11535 | miR-322-5p | Fam164a | 67306 | ||
Kit | 16590 | miR-669e-3p | Tia1 | 21841 | miR-326-5p | Aif1l | 108897 | |
Serpinb1b | 282663 | Fgf13 | 14168 | miR-335-5p | Gclc | 14629 | ||
Trim59 | 66949 | Pak3 | 18481 | miR-3473d | B4galt6 | 56386 | ||
Bmper | 73230 | miR-101a-3p | Sult4a1 | 29859 | miR-363-3p | Adm | 11535 | |
miR-30a-5p | Prr11 | 270906 | Mbnl3 | 171170 | miR-376c-5p | Prrx1 | 18933 | |
Cysltr1 | 58861 | miR-101a-5p | Klhl13 | 67455 | miR-378-3p | Sema3e | 20349 | |
Gnai1 | 14677 | Mbnl3 | 171170 | miR-378b | Igf2bp3 | 140488 | ||
Rnf219 | 72486 | miR-101b-3p | Sult4a1 | 29859 | miR-380-3p | Mbnl3 | 171170 | |
Nedd4l | 83814 | Mbnl3 | 171170 | miR-382-3p | Sdpr | 20324 | ||
miR-30e-5p | Prr11 | 270906 | miR-105 | Ect2 | 13605 | miR-409-3p | Akr1c14 | 105387 |
Cysltr1 | 58861 | Zfpm2 | 22762 | miR-431-5p | Klf15 | 66277 | ||
Gnai1 | 14677 | miR-142-5p | Depdc1a | 76131 | miR-463-5p | Pla2r1 | 18779 | |
Lox | 16948 | Igf2bp3 | 140488 | miR-466i-5p | Dcdc2a | 195208 | ||
Rnf219 | 72486 | miR-181b-1-3p | Fgf13 | 14168 | miR-466 l-3p | Snhg11 | 319317 | |
miR-543-3p | Mlf1 | 17349 | Slc1a2 | 20511 | miR-470-5p | Steap4 | 117167 | |
Slc1a2 | 20511 | miR-1912-3p | Gpr137b | 83924 | miR-484 | Csf1 | 12977 | |
Cysltr1 | 58861 | Ptchd1 | 211612 | miR-496-3p | Tspan8 | 216350 | ||
Fut4 | 14345 | miR-1942 | Mxra8 | 74761 | miR-499-5p | Cdk1 | 12534 | |
Kifc2 | 16581 | Zfpm2 | 22762 | miR-5101 | Il5ra | 16192 | ||
let-7a-2-3p | 4930486L24Rik | 214639 | miR-1a-1-5p | Ehf | 13661 | miR-5125 | Mllt11 | 56772 |
Sema3e | 20349 | Dcdc2a | 195208 | miR-5127 | Col4a5 | 12830 | ||
Cd24a | 12484 | miR-1b-5p | Ugt2b35 | 243085 | miR-5133 | Rasl12 | 70784 | |
Pamr1 | 210622 | Tlr4 | 21898 | miR-544-3p | Snhg11 | 319317 | ||
miR-137-3p | Glis2 | 83396 | miR-219-5p | Tnfsf15 | 326623 | miR-675-3p | Mbnl3 | 171170 |
Nfasc | 269116 | Gprc5b | 64297 | miR-677-5p | Gclc | 14629 | ||
Cep55 | 74107 | miR-26a-5p | Hpgd | 15446 | miR-712-5p | Cep55 | 74107 | |
Birc5 | 11799 | Rgs4 | 19736 | miR-7a-5p | Mlph | 171531 | ||
miR-149-5p | B4galt6 | 56386 | miR-294-3p | Lass3 | 545975 | miR-877-3p | Npr3 | 18162 |
Pak3 | 18481 | Zfpm2 | 22762 | miR-879-5p | Hmmr | 15366 | ||
Il5ra | 16192 | miR-29a-3p | Col5a3 | 53867 | miR-881-3p | Ehf | 13661 | |
Axl | 26362 | Ppic | 19038 | |||||
miR-194-5p | Gas2l3 | 237436 | miR-3066-5p | Gpt2 | 108682 | |||
Fam164a | 67306 | Ccna2 | 12428 | |||||
Ppic | 19038 | miR-3071-5p | Igf2bp1 | 140486 | ||||
Trim59 | 66949 | Mbnl3 | 171170 | |||||
miR-1964-5p | Csdc2 | 105859 | miR-204-3p | Kirrel3 | 67703 | miR-465c-5p | Ugt2b1 | 71773 |
Kirrel3 | 67703 | miR-23a-3p | Cyp3a11 | 13112 | miR-466b-3p | Oas3 | 246727 | |
let-7e-5p | Cyp2c50 | 107141 | miR-295-5p | Aldob | 230163 | miR-466f-3p | Npat | 244879 |
miR-126-5p | Ugt3a2 | 223337 | miR-30e-3p | Cyp2f2 | 13107 | miR-466 m-3p | Oas3 | 246727 |
miR-181a-5p | Nipal1 | 70701 | miR-328-5p | Cyp2d22 | 56448 | miR-5131 | Ccdc85b | 240514 |
miR-181b-5p | Nipal1 | 70701 | miR-344f-5p | Scd1 | 20249 | miR-551b-5p | 5033411D12Rik | 192136 |
miR-1960 | Mrc1 | 17533 | miR-3470a | Dnahc17 | 69926 | miR-676-5p | Slc27a5 | 26459 |
miR-19b-1-5p | Npat | 244879 | miR-465a-5p | Ugt2b1 | 71773 | miR-707 | Slco1a1 | 28248 |
Pathway analysis of putative microRNA targets
Pathways from temporal up-pattern (KEGG ID) | P-value* | FDR** | Pathways from temporal down-pattern (KEGG ID) | P-value | FDR | ||
---|---|---|---|---|---|---|---|
All genes | Simple enrichment analysis | Cell cycle (mmu04110) | 8.41E-05 | 9.62E-03 | Drug metabolism-cytochrome P450 (mmu00982) | 3.57E-10 | 3.07E-08 |
Systemic lupus erythematosus (mmu05322) | 7.97E-10 | 3.43E-08 | |||||
Complement and coagulation cascades (mmu04610) | 3.45E-08 | 9.88E-07 | |||||
Retinol metabolism (mmu00830) | 4.38E-08 | 9.41E-07 | |||||
Metabolism of xenobiotics by cytochrome P450 (mmu00980) | 1.15E-06 | 1.97E-05 | |||||
Linoleic acid metabolism (mmu00591) | 2.04E-06 | 2.92E-05 | |||||
Prion diseases (mmu05020) | 2.43E-05 | 2.99E-04 | |||||
PPAR signaling pathway (mmu03320) | 3.42E-05 | 3.67E-04 | |||||
Drug metabolism-other enzymes (mmu00983) | 4.87E-04 | 4.64E-03 | |||||
Topology-based signaling pathway analysis | Systemic lupus erythematosus (mmu05322) | 1.74E-10 | 1.36E-08 | ||||
Complement and coagulation cascades (mmu04610) | 4.55E-10 | 1.77E-08 | |||||
Cytokine-cytokine receptor interaction (mmu04060) | 1.69E-08 | 1.84E-06 | Prion diseases (mmu05020) | 2.82E-07 | 7.33E-06 | ||
Osteoclast differentiation (mmu04380) | 4.88E-06 | 2.66E-04 | PPAR signaling pathway (mmu03320) | 1.42E-06 | 2.78E-05 | ||
Cell cycle (mmu04110) | 1.52E-04 | 5.55E-03 | Staphylococcus aureus infection (mmu05150) | 3.48E-06 | 5.42E-05 | ||
Serotonergic synapse (mmu04726) | 1.18E-05 | 1.53E-04 | |||||
Alcoholism (mmu05034) | 2.48E-04 | 2.77E-03 | |||||
Endocrine and other factor-regulated calcium reabsorption (mmu04961) | 7.76E-04 | 7.57E-03 | |||||
MicroRNA targets | Simple enrichment analysis | No pathway | Metabolism of xenobiotics by cytochrome P450 (mmu00980) | 1.45E-04 | 3.19E-03 | ||
Topology-based signaling pathway analysis | Cell cycle (mmu04110) | 5.46E-03 | 1.00E-02 | No pathway | |||
Non-microRNA targets | Simple enrichment analysis | No pathway | Systemic lupus erythematosus (mmu05322) | 1.63E-10 | 1.22E-08 | ||
Complement and coagulation cascades (mmu04610) | 9.24E-09 | 3.46E-07 | |||||
Drug metabolism (mmu00982) | 1.94E-07 | 4.85E-06 | |||||
Prion diseases (mmu05020) | 1.20E-05 | 2.26E-04 | |||||
Retinol metabolism (mmu00830) | 2.82E-05 | 4.22E-04 | |||||
Linoleic acid metabolism (mmu00591) | 2.01E-04 | 2.51E-03 | |||||
PPAR signaling pathway (mmu03320) | 8.76E-04 | 9.34E-03 | |||||
Topology-based signaling pathway analysis | Cytokine-cytokine receptor interaction (mmu04060) | 1.63E-07 | 1.42E-05 | Systemic lupus erythematosus (mmu05322) | 3.95E-11 | 3.00E-09 | |
Complement and coagulation cascades (mmu04610) | 1.31E-10 | 4.97E-09 | |||||
Prion diseases (mmu05020) | 1.32E-07 | 3.34E-06 | |||||
NF-kappa B signaling pathway (mmu04064) | 2.37E-05 | 8.95E-04 | Staphylococcus aureus infection (mmu05150) | 1.63E-06 | 3.10E-05 | ||
MAPK signaling pathway (mmu04010) | 3.09E-05 | 8.95E-04 | Serotonergic synapse (mmu04726) | 5.15E-05 | 7.83E-04 | ||
Osteoclast differentiation (mmu04380) | 4.17E-04 | 9.07E-03 | PPAR signaling pathway (mmu03320) | 9.33E-05 | 1.18E-03 | ||
Endocrine and other factor-regulated calcium reabsorption (mmu04961) | 6.65E-04 | 7.22E-03 | |||||
Alcoholism (mmu05034) | 9.07E-04 | 8.61E-03 |