Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRXJ9UN)

• DOT Name: Perilipin-2 (PLIN2)
• Synonyms: Adipophilin; Adipose differentiation-related protein; ADRP
• Gene Name: PLIN2
• Related Disease:
  Matthew-Wood syndrome
  Metabolic disorder
  Pancreatic ductal carcinoma
  Advanced cancer
  Alzheimer disease
  Atrial fibrillation
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Burkitt lymphoma
  Clear cell renal carcinoma
  Diabetic kidney disease
  Dilated cardiomyopathy 1A
  Fatty liver disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Hyperglycemia
  Hyperinsulinemia
  Kidney cancer
  Lung adenocarcinoma
  Neoplasm
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Obesity
  Osteoporosis
  Renal carcinoma
  Renal cell carcinoma
  Retinitis pigmentosa
  Sarcoma
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uterine fibroids
  Choriocarcinoma
  Malignant soft tissue neoplasm
  Squamous cell carcinoma
  Arteriosclerosis
  Atherosclerosis
  Colon adenocarcinoma
  Coronary heart disease
  Cutaneous melanoma
  Fetal growth restriction
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Melanoma
  Type-1/2 diabetes
• UniProt ID: PLIN2_HUMAN
• Pfam ID: PF03036
• Sequence:
  MASVAVDPQPSVVTRVVNLPLVSSTYDLMSSAYLSTKDQYPYLKSVCEMAENGVKTITSV
  AMTSALPIIQKLEPQIAVANTYACKGLDRIEERLPILNQPSTQIVANAKGAVTGAKDAVT
  TTVTGAKDSVASTITGVMDKTKGAVTGSVEKTKSVVSGSINTVLGSRMMQLVSSGVENAL
  TKSELLVEQYLPLTEEELEKEAKKVEGFDLVQKPSYYVRLGSLSTKLHSRAYQQALSRVK
  EAKQKSQQTISQLHSTVHLIEFARKNVYSANQKIQDAQDKLYLSWVEWKRSIGYDDTDES
  HCAEHIESRTLAIARNLTQQLQTTCHTLLSNIQGVPQNIQDQAKHMGVMAGDIYSVFRNA
  ASFKEVSDSLLTSSKGQLQKMKESLDDVMDYLVNNTPLNWLVGPFYPQLTESQNAQDQGA
  EMDKSSQETQRSEHKTH
• Function: Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets.
• Tissue Specificity: Milk lipid globules.
• KEGG Pathway: PPAR sig.ling pathway (hsa03320)
• Reactome Pathway:
  Lipophagy (R-HSA-9613354)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[1]
Metabolic disorder	DIS71G5H	Definitive	Biomarker	[2]
Pancreatic ductal carcinoma	DIS26F9Q	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[4]
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Burkitt lymphoma	DIS9D5XU	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[9]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[14]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[15]
Kidney cancer	DISBIPKM	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[11]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[14]
Obesity	DIS47Y1K	Strong	Genetic Variation	[18]
Osteoporosis	DISF2JE0	Strong	Altered Expression	[19]
Renal carcinoma	DISER9XT	Strong	Biomarker	[3]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[20]
Sarcoma	DISZDG3U	Strong	Altered Expression	[21]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[23]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[24]
Malignant soft tissue neoplasm	DISTC6NO	moderate	Altered Expression	[21]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[25]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[26]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[26]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[27]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[28]
Cutaneous melanoma	DIS3MMH9	Limited	Altered Expression	[29]
Fetal growth restriction	DIS5WEJ5	Limited	Biomarker	[30]
Gastric cancer	DISXGOUK	Limited	Biomarker	[31]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[31]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[29]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[32]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Perilipin-2 (PLIN2) affects the response to substance of Fluorouracil.	[71]

3 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 Perilipin-2 (PLIN2).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Perilipin-2 (PLIN2).	[56]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Perilipin-2 (PLIN2).	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Perilipin-2 (PLIN2).	[34]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Perilipin-2 (PLIN2).	[35]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Perilipin-2 (PLIN2).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Perilipin-2 (PLIN2).	[37]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Perilipin-2 (PLIN2).	[38]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Perilipin-2 (PLIN2).	[39]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Perilipin-2 (PLIN2).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Perilipin-2 (PLIN2).	[41]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Perilipin-2 (PLIN2).	[42]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Perilipin-2 (PLIN2).	[31]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Perilipin-2 (PLIN2).	[44]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Perilipin-2 (PLIN2).	[45]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Perilipin-2 (PLIN2).	[46]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Perilipin-2 (PLIN2).	[47]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Perilipin-2 (PLIN2).	[48]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Perilipin-2 (PLIN2).	[49]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Perilipin-2 (PLIN2).	[50]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Perilipin-2 (PLIN2).	[47]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Perilipin-2 (PLIN2).	[51]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Perilipin-2 (PLIN2).	[48]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid increases the expression of Perilipin-2 (PLIN2).	[52]
Ciprofibrate	DMGC5DB	Approved	Ciprofibrate increases the expression of Perilipin-2 (PLIN2).	[53]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Perilipin-2 (PLIN2).	[54]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Perilipin-2 (PLIN2).	[55]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Perilipin-2 (PLIN2).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Perilipin-2 (PLIN2).	[58]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Perilipin-2 (PLIN2).	[50]
GW-501516	DMPL2KM	Discontinued in Phase 4	GW-501516 increases the expression of Perilipin-2 (PLIN2).	[53]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of Perilipin-2 (PLIN2).	[60]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Perilipin-2 (PLIN2).	[50]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Perilipin-2 (PLIN2).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Perilipin-2 (PLIN2).	[61]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Perilipin-2 (PLIN2).	[62]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Perilipin-2 (PLIN2).	[63]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Perilipin-2 (PLIN2).	[64]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Perilipin-2 (PLIN2).	[65]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Perilipin-2 (PLIN2).	[66]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Perilipin-2 (PLIN2).	[67]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Perilipin-2 (PLIN2).	[68]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Perilipin-2 (PLIN2).	[69]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Perilipin-2 (PLIN2).	[69]
Fibrates	DMFNTMY	Investigative	Fibrates increases the expression of Perilipin-2 (PLIN2).	[70]
GW0742X	DMGKEO5	Investigative	GW0742X increases the expression of Perilipin-2 (PLIN2).	[50]

References

• [1] Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis.Pancreatology. 2019 Apr;19(3):443-448. doi: 10.1016/j.pan.2019.03.001. Epub 2019 Mar 11.
• [2] Perilipin 2 and Age-Related Metabolic Diseases: A New Perspective.Trends Endocrinol Metab. 2016 Dec;27(12):893-903. doi: 10.1016/j.tem.2016.09.001. Epub 2016 Sep 19.
• [3] Bioplasmonic paper-based assay for perilipin-2 non-invasively detects renal cancer.Kidney Int. 2019 Dec;96(6):1417-1421. doi: 10.1016/j.kint.2019.08.020. Epub 2019 Sep 3.
• [4] Whole exome sequence-based association analyses of plasma amyloid- in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.PLoS One. 2017 Jul 13;12(7):e0180046. doi: 10.1371/journal.pone.0180046. eCollection 2017.
• [5] Cardiac overexpression of perilipin 2 induces atrial steatosis, connexin 43 remodeling, and atrial fibrillation in aged mice.Am J Physiol Endocrinol Metab. 2019 Dec 1;317(6):E1193-E1204. doi: 10.1152/ajpendo.00227.2019. Epub 2019 Oct 29.
• [6] The significance of lipid accumulation in breast carcinoma cells through perilipin 2 and its clinicopathological significance.Pathol Int. 2019 Aug;69(8):463-471. doi: 10.1111/pin.12831. Epub 2019 Jul 4.
• [7] The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: adipophilin.PLoS One. 2012;7(8):e44315. doi: 10.1371/journal.pone.0044315. Epub 2012 Aug 31.
• [8] Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease.Clin Sci (Lond). 2018 Nov 21;132(22):2407-2422. doi: 10.1042/CS20180702. Print 2018 Nov 30.
• [9] Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.Histopathology. 2013 Oct;63(4):509-19. doi: 10.1111/his.12172. Epub 2013 Aug 14.
• [10] Pharmacological Inhibition of CCR2/5 Signaling Prevents and Reverses Alcohol-Induced Liver Damage, Steatosis, and Inflammation in Mice.Hepatology. 2019 Mar;69(3):1105-1121. doi: 10.1002/hep.30249. Epub 2019 Feb 12.
• [11] Cannabinoid receptor 1 knockout alleviates hepatic steatosis by downregulating perilipin 2.Lab Invest. 2020 Mar;100(3):454-465. doi: 10.1038/s41374-019-0327-5. Epub 2019 Sep 30.
• [12] Perilipin-2 is critical for efficient lipoprotein and hepatitis C virus particle production.J Cell Sci. 2019 Jan 9;132(1):jcs217042. doi: 10.1242/jcs.217042.
• [13] Hepatitis B virus X induces inflammation and cancer in mice liver through dysregulation of cytoskeletal remodeling and lipid metabolism.Oncotarget. 2016 Oct 25;7(43):70559-70574. doi: 10.18632/oncotarget.12372.
• [14] Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in -cells.J Cell Mol Med. 2019 Apr;23(4):2890-2900. doi: 10.1111/jcmm.14172. Epub 2019 Feb 1.
• [15] The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects.Diabetes Metab Res Rev. 2016 Sep;32(6):550-6. doi: 10.1002/dmrr.2751. Epub 2015 Nov 11.
• [16] Adipophilin expression in lung adenocarcinoma is associated with apocrine-like features and poor clinical prognosis: an immunohistochemical study of 328 cases.Histopathology. 2017 Jan;70(2):232-241. doi: 10.1111/his.13048. Epub 2016 Sep 27.
• [17] Cytologic Grading of Cutaneous Sebaceous Neoplasms: Does it Help to Differentiate Benign From Malignant?.Am J Dermatopathol. 2019 Oct;41(10):722-732. doi: 10.1097/DAD.0000000000001434.
• [18] Perilipin-2 promotes obesity and progressive fatty liver disease in mice through mechanistically distinct hepatocyte and extra-hepatocyte actions.J Physiol. 2019 Mar;597(6):1565-1584. doi: 10.1113/JP277140. Epub 2019 Jan 2.
• [19] Osteoblastogenesis and adipogenesis are higher in osteoarthritic than in osteoporotic bone tissue.Arch Med Res. 2011 Jul;42(5):392-7. doi: 10.1016/j.arcmed.2011.08.005. Epub 2011 Aug 18.
• [20] Mutations in known genes account for 58% of autosomal dominant retinitis pigmentosa (adRP).Adv Exp Med Biol. 2008;613:203-9. doi: 10.1007/978-0-387-74904-4_23.
• [21] Perilipin 1 is a highly specific marker for adipocytic differentiation in sarcomas with intermediate sensitivity.J Cancer Res Clin Oncol. 2017 Feb;143(2):225-232. doi: 10.1007/s00432-016-2263-8. Epub 2016 Sep 19.
• [22] A Novel Topical PPAR Agonist Induces PPAR Activity in Ulcerative Colitis Mucosa and Prevents and Reverses Inflammation in Induced Colitis Models.Inflamm Bowel Dis. 2018 Mar 19;24(4):792-805. doi: 10.1093/ibd/izx079.
• [23] PLIN2 Functions As a Novel Link Between Progesterone Signaling and Metabolism in Uterine Leiomyoma Cells.J Clin Endocrinol Metab. 2019 Dec 1;104(12):6256-6264. doi: 10.1210/jc.2019-00762.
• [24] Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line.J Lipid Res. 2006 Apr;47(4):815-23. doi: 10.1194/jlr.M500527-JLR200. Epub 2006 Jan 3.
• [25] Sebaceous gland carcinoma of the ocular adnexa - variability in clinical and histological appearance with analysis of immunohistochemical staining patterns.Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2277-2285. doi: 10.1007/s00417-017-3738-2. Epub 2017 Jul 24.
• [26] Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.J Intern Med. 2019 Dec;286(6):660-675. doi: 10.1111/joim.12951. Epub 2019 Jul 29.
• [27] Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets.Mol Cell Biol. 2019 Apr 16;39(9):e00374-18. doi: 10.1128/MCB.00374-18. Print 2019 May 1.
• [28] Perilipin 2 levels are increased in patients with in-stent neoatherosclerosis: A clue to mechanisms of accelerated plaque formation after drug-eluting stent implantation.Int J Cardiol. 2018 May 1;258:55-58. doi: 10.1016/j.ijcard.2018.01.074.
• [29] Adipophilin expression in cutaneous malignant melanoma.J Cutan Pathol. 2017 Mar;44(3):228-236. doi: 10.1111/cup.12868. Epub 2016 Dec 22.
• [30] Alterations in placental long chain polyunsaturated fatty acid metabolism in human intrauterine growth restriction.Clin Sci (Lond). 2018 Mar 15;132(5):595-607. doi: 10.1042/CS20171340. Print 2018 Mar 15.
• [31] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [32] PLIN2 is a Key Regulator of the Unfolded Protein Response and Endoplasmic Reticulum Stress Resolution in Pancreatic Cells.Sci Rep. 2017 Jan 19;7:40855. doi: 10.1038/srep40855.
• [33] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [34] Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo models. Arch Toxicol. 2015 Dec;89(12):2325-37. doi: 10.1007/s00204-014-1365-9. Epub 2014 Sep 17.
• [35] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [36] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [37] 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.
• [38] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [39] 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.
• [40] 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.
• [41] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [42] Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumatic drugs. J Biomol Screen. 2007 Apr;12(3):328-40. doi: 10.1177/1087057107299261. Epub 2007 Mar 22.
• [43] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [44] 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.
• [45] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [46] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [47] 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.
• [48] Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation. Biochem Biophys Res Commun. 2004 Oct 22;323(3):782-8.
• [49] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [50] Regulation of peroxisome proliferator-activated receptor-beta/delta by the APC/beta-CATENIN pathway and nonsteroidal antiinflammatory drugs. Mol Carcinog. 2009 Oct;48(10):942-52. doi: 10.1002/mc.20546.
• [51] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [52] Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines. J Clin Biochem Nutr. 2010 Jul;47(1):81-90.
• [53] Role of Peroxisome Proliferator-Activated Receptor / and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells. PPAR Res. 2013;2013:121956. doi: 10.1155/2013/121956. Epub 2013 May 2.
• [54] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [55] MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2006 Aug;20(5):736-42.
• [56] 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.
• [57] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [58] 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.
• [59] 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.
• [60] Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response. BMC Genomics. 2008 Jun 2;9:262. doi: 10.1186/1471-2164-9-262.
• [61] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [62] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [63] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [64] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [65] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.
• [66] Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
• [67] 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.
• [68] PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. Toxicol Appl Pharmacol. 2014 Apr 1;276(1):73-81. doi: 10.1016/j.taap.2014.02.001. Epub 2014 Feb 15.
• [69] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.
• [70] Decrease of hepatic stellate cells in rats with enhanced sensitivity to clofibrate-induced hepatocarcinogenesis. Cancer Sci. 2011 Apr;102(4):735-41. doi: 10.1111/j.1349-7006.2011.01856.x. Epub 2011 Feb 10.
• [71] 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.