Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCVRDDX)

• DOT Name: A-kinase anchor protein 12 (AKAP12)
• Synonyms: AKAP-12; A-kinase anchor protein 250 kDa; AKAP 250; Gravin; Myasthenia gravis autoantigen
• Gene Name: AKAP12
• Related Disease:
  Chronic kidney disease
  Acute leukaemia
  Acute myelogenous leukaemia
  Acute myocardial infarction
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Benign prostatic hyperplasia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Cardiac failure
  Colon cancer
  Colorectal carcinoma
  Congestive heart failure
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric neoplasm
  Glioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Metastatic melanoma
  Myelodysplastic syndrome
  Myocardial infarction
  Neoplasm
  Neoplasm of esophagus
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Retinoblastoma
  Sciatic neuropathy
  Squamous cell carcinoma
  Stomach cancer
  Chronic obstructive pulmonary disease
  Meningioma
  Pancreatic ductal carcinoma
  Rheumatoid arthritis
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Liver cirrhosis
  Small lymphocytic lymphoma
• UniProt ID: AKA12_HUMAN
• Pfam ID: PF10522 ; PF03832
• Sequence:
  MGAGSSTEQRSPEQPPEGSSTPAEPEPSGGGPSAEAAPDTTADPAIAASDPATKLLQKNG
  QLSTINGVAEQDELSLQEGDLNGQKGALNGQGALNSQEEEEVIVTEVGQRDSEDVSKRDS
  DKEMATKSAVVHDITDDGQEETPEIIEQIPSSESNLEELTQPTESQANDIGFKKVFKFVG
  FKFTVKKDKTEKPDTVQLLTVKKDEGEGAAGAGDHKDPSLGAGEAASKESEPKQSTEKPE
  ETLKREQSHAEISPPAESGQAVEECKEEGEEKQEKEPSKSAESPTSPVTSETGSTFKKFF
  TQGWAGWRKKTSFRKPKEDEVEASEKKKEQEPEKVDTEEDGKAEVASEKLTASEQAHPQE
  PAESAHEPRLSAEYEKVELPSEEQVSGSQGPSEEKPAPLATEVFDEKIEVHQEEVVAEVH
  VSTVEERTEEQKTEVEETAGSVPAEELVEMDAEPQEAEPAKELVKLKETCVSGEDPTQGA
  DLSPDEKVLSKPPEGVVSEVEMLSSQERMKVQGSPLKKLFTSTGLKKLSGKKQKGKRGGG
  DEESGEHTQVPADSPDSQEEQKGESSASSPEEPEEITCLEKGLAEVQQDGEAEEGATSDG
  EKKREGVTPWASFKKMVTPKKRVRRPSESDKEDELDKVKSATLSSTESTASEMQEEMKGS
  VEEPKPEEPKRKVDTSVSWEALICVGSSKKRARRGSSSDEEGGPKAMGGDHQKADEAGKD
  KETGTDGILAGSQEHDPGQGSSSPEQAGSPTEGEGVSTWESFKRLVTPRKKSKSKLEEKS
  EDSIAGSGVEHSTPDTEPGKEESWVSIKKFIPGRRKKRPDGKQEQAPVEDAGPTGANEDD
  SDVPAVVPLSEYDAVEREKMEAQQAQKSAEQPEQKAATEVSKELSESQVHMMAAAVADGT
  RAATIIEERSPSWISASVTEPLEQVEAEAALLTEEVLEREVIAEEEPPTVTEPLPENREA
  RGDTVVSEAELTPEAVTAAETAGPLGAEEGTEASAAEETTEMVSAVSQLTDSPDTTEEAT
  PVQEVEGGVPDIEEQERRTQEVLQAVAEKVKEESQLPGTGGPEDVLQPVQRAEAERPEEQ
  AEASGLKKETDVVLKVDAQEAKTEPFTQGKVVGQTTPESFEKAPQVTESIESSELVTTCQ
  AETLAGVKSQEMVMEQAIPPDSVETPTDSETDGSTPVADFDAPGTTQKDEIVEIHEENEV
  ASGTQSGGTEAEAVPAQKERPPAPSSFVFQEETKEQSKMEDTLEHTDKEVSVETVSILSK
  TEGTQEADQYADEKTKDVPFFEGLEGSIDTGITVSREKVTEVALKGEGTEEAECKKDDAL
  ELQSHAKSPPSPVEREMVVQVEREKTEAEPTHVNEEKLEHETAVTVSEEVSKQLLQTVNV
  PIIDGAKEVSSLEGSPPPCLGQEEAVCTKIQVQSSEASFTLTAAAEEEKVLGETANILET
  GETLEPAGAHLVLEEKSSEKNEDFAAHPGEDAVPTGPDCQAKSTPVIVSATTKKGLSSDL
  EGEKTTSLKWKSDEVDEQVACQEVKVSVAIEDLEPENGILELETKSSKLVQNIIQTAVDQ
  FVRTEETATEMLTSELQTQAHVIKADSQDAGQETEKEGEEPQASAQDETPITSAKEESES
  TAVGQAHSDISKDMSEASEKTMTVEVEGSTVNDQQLEEVVLPSEEEGGGAGTKSVPEDDG
  HALLAERIEKSLVEPKEDEKGDDVDDPENQNSALADTDASGGLTKESPDTNGPKQKEKED
  AQEVELQEGKVHSESDKAITPQAQEELQKQERESAKSELTES
• Function: Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
• Tissue Specificity: Expressed in endothelial cells, cultured fibroblasts and osteosarcoma, but not in platelets, leukocytes, monocytic cell lines or peripherical blood cells.
• Reactome Pathway:
  RHOF GTPase cycle (R-HSA-9035034)
  RHOD GTPase cycle (R-HSA-9013405)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Definitive	Biomarker	[1]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[3]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Biomarker	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Benign prostatic hyperplasia	DISI3CW2	Strong	Posttranslational Modification	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[11]
Cardiac failure	DISDC067	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Altered Expression	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[14]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[11]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[11]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[15]
Glioma	DIS5RPEH	Strong	Posttranslational Modification	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[16]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[17]
Lung carcinoma	DISTR26C	Strong	Posttranslational Modification	[17]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[18]
Metastatic melanoma	DISSL43L	Strong	Biomarker	[19]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[20]
Myocardial infarction	DIS655KI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[11]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[22]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[14]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[14]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[23]
Sciatic neuropathy	DISMGDKX	Strong	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[11]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[15]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[25]
Meningioma	DISPT4TG	moderate	Biomarker	[26]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Posttranslational Modification	[27]
Rheumatoid arthritis	DISTSB4J	Disputed	Genetic Variation	[28]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[16]
Liver cancer	DISDE4BI	Limited	Biomarker	[16]
Liver cirrhosis	DIS4G1GX	Limited	Biomarker	[29]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[30]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	A-kinase anchor protein 12 (AKAP12) affects the response to substance of Etoposide.	[68]
Mitomycin	DMH0ZJE	Approved	A-kinase anchor protein 12 (AKAP12) affects the response to substance of Mitomycin.	[68]

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of A-kinase anchor protein 12 (AKAP12).	[31]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of A-kinase anchor protein 12 (AKAP12).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of A-kinase anchor protein 12 (AKAP12).	[58]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of A-kinase anchor protein 12 (AKAP12).	[61]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of A-kinase anchor protein 12 (AKAP12).	[61]

34 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of A-kinase anchor protein 12 (AKAP12).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of A-kinase anchor protein 12 (AKAP12).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of A-kinase anchor protein 12 (AKAP12).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of A-kinase anchor protein 12 (AKAP12).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of A-kinase anchor protein 12 (AKAP12).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of A-kinase anchor protein 12 (AKAP12).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of A-kinase anchor protein 12 (AKAP12).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of A-kinase anchor protein 12 (AKAP12).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of A-kinase anchor protein 12 (AKAP12).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of A-kinase anchor protein 12 (AKAP12).	[41]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of A-kinase anchor protein 12 (AKAP12).	[42]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of A-kinase anchor protein 12 (AKAP12).	[43]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of A-kinase anchor protein 12 (AKAP12).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of A-kinase anchor protein 12 (AKAP12).	[45]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of A-kinase anchor protein 12 (AKAP12).	[47]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of A-kinase anchor protein 12 (AKAP12).	[48]
Menadione	DMSJDTY	Approved	Menadione affects the expression of A-kinase anchor protein 12 (AKAP12).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of A-kinase anchor protein 12 (AKAP12).	[49]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of A-kinase anchor protein 12 (AKAP12).	[50]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of A-kinase anchor protein 12 (AKAP12).	[51]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of A-kinase anchor protein 12 (AKAP12).	[52]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of A-kinase anchor protein 12 (AKAP12).	[53]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of A-kinase anchor protein 12 (AKAP12).	[54]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of A-kinase anchor protein 12 (AKAP12).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of A-kinase anchor protein 12 (AKAP12).	[56]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of A-kinase anchor protein 12 (AKAP12).	[57]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of A-kinase anchor protein 12 (AKAP12).	[59]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of A-kinase anchor protein 12 (AKAP12).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of A-kinase anchor protein 12 (AKAP12).	[62]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of A-kinase anchor protein 12 (AKAP12).	[63]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of A-kinase anchor protein 12 (AKAP12).	[64]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of A-kinase anchor protein 12 (AKAP12).	[65]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of A-kinase anchor protein 12 (AKAP12).	[66]
Paraoxon	DMN4ZKC	Investigative	Paraoxon decreases the expression of A-kinase anchor protein 12 (AKAP12).	[67]

References

• [1] Association of gene polymorphisms with chronic kidney disease in Japanese individuals.Int J Mol Med. 2009 Oct;24(4):539-47. doi: 10.3892/ijmm_00000263.
• [2] Gravin gene expression in acute leukaemias: clinical importance and review of the literature.Leuk Lymphoma. 2007 Jun;48(6):1167-72. doi: 10.1080/10428190701377055.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats.J Cardiovasc Transl Res. 2017 Apr;10(2):209-220. doi: 10.1007/s12265-017-9734-4. Epub 2017 Mar 9.
• [5] Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis.Am J Physiol Heart Circ Physiol. 2019 Oct 1;317(4):H793-H810. doi: 10.1152/ajpheart.00215.2019. Epub 2019 Aug 23.
• [6] Differential expression of the tumor suppressor A-kinase anchor protein 12 in human diffuse and pilocytic astrocytomas is regulated by promoter methylation.J Neuropathol Exp Neurol. 2013 Oct;72(10):933-41. doi: 10.1097/NEN.0b013e3182a59a88.
• [7] Quantitative assessment of AKAP12 promoter methylation in human prostate cancer using methylation-sensitive high-resolution melting: correlation with Gleason score.Urology. 2011 Apr;77(4):1006.e1-7. doi: 10.1016/j.urology.2010.12.010. Epub 2011 Feb 18.
• [8] A-kinase anchor protein 12 (AKAP12) inhibits cell migration in breast cancer.Exp Mol Pathol. 2018 Dec;105(3):364-370. doi: 10.1016/j.yexmp.2018.10.010. Epub 2018 Oct 30.
• [9] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [10] The Src-suppressed C kinase substrate, SSeCKS, is a potential metastasis inhibitor in prostate cancer.Cancer Res. 2001 Jul 15;61(14):5644-51.
• [11] Hypermethylation of the AKAP12 promoter is a biomarker of Barrett's-associated esophageal neoplastic progression.Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):111-7. doi: 10.1158/1055-9965.EPI-07-0407.
• [12] Blockage of AKAP12 accelerates angiotensin II (Ang II)-induced cardiac injury in mice by regulating the transforming growth factor 1 (TGF-1) pathway.Biochem Biophys Res Commun. 2018 May 5;499(2):128-135. doi: 10.1016/j.bbrc.2018.02.200. Epub 2018 Mar 6.
• [13] Upregulation of AKAP12 with HDAC3 depletion suppresses the progression and migration of colorectal cancer.Int J Oncol. 2018 Apr;52(4):1305-1316. doi: 10.3892/ijo.2018.4284. Epub 2018 Feb 23.
• [14] Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients.J Proteome Res. 2015 Apr 3;14(4):1900-10. doi: 10.1021/pr5012894. Epub 2015 Mar 19.
• [15] AKAP12/Gravin is inactivated by epigenetic mechanism in human gastric carcinoma and shows growth suppressor activity.Oncogene. 2004 Sep 16;23(42):7095-103. doi: 10.1038/sj.onc.1207932.
• [16] A-kinase anchoring protein 12 is downregulated in human hepatocellular carcinoma and its deficiency in mice aggravates thioacetamide-induced liver injury.Oncol Lett. 2018 Nov;16(5):5907-5915. doi: 10.3892/ol.2018.9396. Epub 2018 Sep 4.
• [17] Methylation of AKAP12{alpha} promoter in lung cancer.Anticancer Res. 2010 Nov;30(11):4595-600.
• [18] RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification.Oncotarget. 2015 Jan 1;6(1):116-29. doi: 10.18632/oncotarget.2699.
• [19] SSeCKS/Akap12 suppresses metastatic melanoma lung colonization by attenuating Src-mediated pre-metastatic niche crosstalk.Oncotarget. 2018 Sep 11;9(71):33515-33527. doi: 10.18632/oncotarget.26067. eCollection 2018 Sep 11.
• [20] Downregulation of microRNA-144 inhibits proliferation and promotes the apoptosis of myelodysplastic syndrome cells through the activation of the AKAP12-dependent ERK1/2 signaling pathway.Cell Signal. 2020 Apr;68:109493. doi: 10.1016/j.cellsig.2019.109493. Epub 2019 Dec 3.
• [21] Identification of risk genes associated with myocardial infarction based on the recursive feature elimination algorithm and support vector machine classifier.Mol Med Rep. 2018 Jan;17(1):1555-1560. doi: 10.3892/mmr.2017.8044. Epub 2017 Nov 14.
• [22] Silencing of Cited2 and Akap12 genes in radiation-induced rat osteosarcomas.Biochem Biophys Res Commun. 2009 Dec 18;390(3):654-8. doi: 10.1016/j.bbrc.2009.10.022. Epub 2009 Oct 13.
• [23] AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha.J Neurosci. 2007 Apr 18;27(16):4472-81. doi: 10.1523/JNEUROSCI.5368-06.2007.
• [24] A critical role of SRC-suppressed C kinase substrate in rat astrocytes after chronic constriction injury.Neuromolecular Med. 2010 Sep;12(3):205-16. doi: 10.1007/s12017-009-8093-y. Epub 2009 Nov 25.
• [25] A-kinase-anchoring proteins coordinate inflammatory responses to cigarette smoke in airway smooth muscle.Am J Physiol Lung Cell Mol Physiol. 2015 Apr 15;308(8):L766-75. doi: 10.1152/ajplung.00301.2014. Epub 2015 Jan 30.
• [26] Kinome and phosphoproteome of high-grade meningiomas reveal AKAP12 as a central regulator of aggressiveness and its possible role in progression.Sci Rep. 2018 Feb 1;8(1):2098. doi: 10.1038/s41598-018-19308-y.
• [27] SERPINB5 and AKAP12 - expression and promoter methylation of metastasis suppressor genes in pancreatic ductal adenocarcinoma.BMC Cancer. 2010 Oct 12;10:549. doi: 10.1186/1471-2407-10-549.
• [28] Deduction of Novel Genes Potentially Involved in Osteoblasts of Rheumatoid Arthritis Using Next-Generation Sequencing and Bioinformatic Approaches.Int J Mol Sci. 2017 Nov 11;18(11):2396. doi: 10.3390/ijms18112396.
• [29] Increased SSeCKS expression in rat hepatic stellate cells upon activation in vitro and in vivo.Inflammation. 2013 Dec;36(6):1415-23. doi: 10.1007/s10753-013-9681-4.
• [30] Identification of key miRNA-gene pairs in chronic lymphocytic leukemia through integrated analysis of mRNA and miRNA microarray.Oncol Lett. 2018 Jan;15(1):361-367. doi: 10.3892/ol.2017.7287. Epub 2017 Oct 30.
• [31] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [32] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [33] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [34] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [35] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [36] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [37] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [38] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [39] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [40] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [41] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [42] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [43] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [44] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [45] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [46] Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy. J Mol Med (Berl). 2007 Oct;85(10):1137-48. doi: 10.1007/s00109-007-0216-z. Epub 2007 Jun 15.
• [47] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [48] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [49] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [50] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [51] Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001 Dec;60(6):1288-95. doi: 10.1124/mol.60.6.1288.
• [52] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [53] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [54] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [55] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [56] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [57] PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature. 2014 Oct 9;514(7521):247-51.
• [58] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [59] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [60] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [61] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [62] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [63] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [64] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [65] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [66] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.
• [67] Genomic and phenotypic alterations of the neuronal-like cells derived from human embryonal carcinoma stem cells (NT2) caused by exposure to organophosphorus compounds paraoxon and mipafox. Int J Mol Sci. 2014 Jan 9;15(1):905-26. doi: 10.3390/ijms15010905.
• [68] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.