Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP8LMCR)

• DOT Name: Rho GTPase-activating protein 7 (DLC1)
• Synonyms: Deleted in liver cancer 1 protein; DLC-1; HP protein; Rho-type GTPase-activating protein 7; START domain-containing protein 12; StARD12; StAR-related lipid transfer protein 12
• Gene Name: DLC1
• Related Disease:
  Lung neoplasm
  Meningioma
  Non-insulin dependent diabetes
  Renal cell carcinoma
  Adenoma
  Adult glioblastoma
  Angiosarcoma
  Arteriosclerosis
  Atherosclerosis
  Benign neoplasm
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Epithelial ovarian cancer
  Gastric neoplasm
  Glioblastoma multiforme
  Head-neck squamous cell carcinoma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Metastatic prostate carcinoma
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Stomach cancer
  Adult lymphoma
  Gastric cancer
  Hereditary diffuse gastric adenocarcinoma
  Lymphoma
  Metastatic malignant neoplasm
  Pancreatic cancer
  Pediatric lymphoma
  Venous thromboembolism
  Carcinoma of liver and intrahepatic biliary tract
  Colorectal carcinoma
  Congenital heart defects, multiple types
  Liver cancer
  Plasma cell myeloma
  Schizophrenia
  Colorectal cancer
• UniProt ID: RHG07_HUMAN
• PDB ID: 2DKY; 2GYT; 2KAP; 2LOZ; 3KUQ; 5FZT
• Pfam ID: PF00620 ; PF07647 ; PF01852
• Sequence:
  MSVAIRKRSWEEHVTHWMGQPFNSDDRNTACHHGLVADSLQASMEKDATLNVDRKEKCVS
  LPDCCHGSELRDFPGRPMGHLSKDVDENDSHEGEDQFLSLEASTETLVHVSDEDNNADLC
  LTDDKQVLNTQGQKTSGQHMIQGAGSLEKALPIIQSNQVSSNSWGIAGETELALVKESGE
  RKVTDSISKSLELCNEISLSEIKDAPKVNAVDTLNVKDIAPEKQLLNSAVIAQQRRKPDP
  PKDENERSTCNVVQNEFLDTPCTNRGLPLLKTDFGSCLLQPPSCPNGMSAENGLEKSGFS
  QHQNKSPPKVKAEDGMQCLQLKETLATQEPTDNQVRLRKRKEIREDRDRARLDSMVLLIM
  KLDQLDQDIENALSTSSSPSGTPTNLRRHVPDLESGSESGADTISVNQTRVNLSSDTEST
  DLPSSTPVANSGTKPKTTAIQGISEKEKAEIEAKEACDWLRATGFPQYAQLYEDFLFPID
  ISLVKREHDFLDRDAIEALCRRLNTLNKCAVMKLEISPHRKRSDDSDEDEPCAISGKWTF
  QRDSKRWSRLEEFDVFSPKQDLVPGSPDDSHPKDGPSPGGTLMDLSERQEVSSVRSLSST
  GSLPSHAPPSEDAATPRTNSVISVCSSSNLAGNDDSFGSLPSPKELSSFSFSMKGHEKTA
  KSKTRSLLKRMESLKLKSSHHSKHKAPSKLGLIISGPILQEGMDEEKLKQLNCVEISALN
  GNRINVPMVRKRSVSNSTQTSSSSSQSETSSAVSTPSPVTRTRSLSACNKRVGMYLEGFD
  PFNQSTFNNVVEQNFKNRESYPEDTVFYIPEDHKPGTFPKALTNGSFSPSGNNGSVNWRT
  GSFHGPGHISLRRENSSDSPKELKRRNSSSSMSSRLSIYDNVPGSILYSSSGDLADLENE
  DIFPELDDILYHVKGMQRIVNQWSEKFSDEGDSDSALDSVSPCPSSPKQIHLDVDNDRTT
  PSDLDSTGNSLNEPEEPSEIPERRDSGVGASLTRSNRHRLRWHSFQSSHRPSLNSVSLQI
  NCQSVAQMNLLQKYSLLKLTALLEKYTPSNKHGFSWAVPKFMKRIKVPDYKDRSVFGVPL
  TVNVQRTGQPLPQSIQQAMRYLRNHCLDQVGLFRKSGVKSRIQALRQMNEGAIDCVNYEG
  QSAYDVADMLKQYFRDLPEPLMTNKLSETFLQIYQYVPKDQRLQAIKAAIMLLPDENREV
  LQTLLYFLSDVTAAVKENQMTPTNLAVCLAPSLFHLNTLKRENSSPRVMQRKQSLGKPDQ
  KDLNENLAATQGLAHMIAECKKLFQVPEEMSRCRNSYTEQELKPLTLEALGHLGNDDSAD
  YQHFLQDCVDGLFKEVKEKFKGWVSYSTSEQAELSYKKVSEGPPLRLWRSVIEVPAVPEE
  ILKRLLKEQHLWDVDLLDSKVIEILDSQTEIYQYVQNSMAPHPARDYVVLRTWRTNLPKG
  ACALLLTSVDHDRAPVVGVRVNVLLSRYLIEPCGPGKSKLTYMCRVDLRGHMPEWYTKSF
  GHLCAAEVVKIRDSFSNQNTETKDTKSR
• Function: Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. Required for growth factor-induced epithelial cell migration; in resting cells, interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex but growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85. The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote RAC1 activation.
• Tissue Specificity: Highest level of expression in the spleen, with rather lower levels in prostate, testis, ovary, small intestine and colon, but none in the thymus.
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung neoplasm	DISVARNB	Definitive	Biomarker	[1]
Meningioma	DISPT4TG	Definitive	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[3]
Renal cell carcinoma	DISQZ2X8	Definitive	Biomarker	[4]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[5]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[6]
Angiosarcoma	DISIYS9W	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[8]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[8]
Benign neoplasm	DISDUXAD	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[10]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[11]
Carcinoma	DISH9F1N	Strong	Altered Expression	[12]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[13]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[14]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[15]
Gastric neoplasm	DISOKN4Y	Strong	Therapeutic	[16]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[17]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[20]
Lung cancer	DISCM4YA	Strong	Biomarker	[21]
Lung carcinoma	DISTR26C	Strong	Biomarker	[21]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[22]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[23]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[24]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[15]
Ovarian neoplasm	DISEAFTY	Strong	Therapeutic	[25]
Prostate cancer	DISF190Y	Strong	Altered Expression	[26]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[26]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[16]
Adult lymphoma	DISK8IZR	moderate	Biomarker	[23]
Gastric cancer	DISXGOUK	moderate	Therapeutic	[16]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	moderate	Therapeutic	[16]
Lymphoma	DISN6V4S	moderate	Biomarker	[23]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[24]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[28]
Pediatric lymphoma	DIS51BK2	moderate	Biomarker	[23]
Venous thromboembolism	DISUR7CR	moderate	Genetic Variation	[29]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Genetic Variation	[30]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[31]
Congenital heart defects, multiple types	DISWZRYW	Limited	Autosomal dominant	[32]
Liver cancer	DISDE4BI	Limited	Genetic Variation	[30]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[33]
Schizophrenia	DISSRV2N	Limited	Genetic Variation	[34]
Colorectal cancer	DISNH7P9	No Known	Unknown	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Rho GTPase-activating protein 7 (DLC1) affects the response to substance of Topotecan.	[59]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Rho GTPase-activating protein 7 (DLC1).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho GTPase-activating protein 7 (DLC1).	[42]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Rho GTPase-activating protein 7 (DLC1).	[43]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Rho GTPase-activating protein 7 (DLC1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Rho GTPase-activating protein 7 (DLC1).	[53]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Rho GTPase-activating protein 7 (DLC1).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rho GTPase-activating protein 7 (DLC1).	[56]

17 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 Rho GTPase-activating protein 7 (DLC1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Rho GTPase-activating protein 7 (DLC1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho GTPase-activating protein 7 (DLC1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Rho GTPase-activating protein 7 (DLC1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Rho GTPase-activating protein 7 (DLC1).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Rho GTPase-activating protein 7 (DLC1).	[41]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Rho GTPase-activating protein 7 (DLC1).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Rho GTPase-activating protein 7 (DLC1).	[46]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Rho GTPase-activating protein 7 (DLC1).	[47]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Rho GTPase-activating protein 7 (DLC1).	[25]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Rho GTPase-activating protein 7 (DLC1).	[49]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Rho GTPase-activating protein 7 (DLC1).	[50]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Rho GTPase-activating protein 7 (DLC1).	[51]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the expression of Rho GTPase-activating protein 7 (DLC1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Rho GTPase-activating protein 7 (DLC1).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Rho GTPase-activating protein 7 (DLC1).	[57]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Rho GTPase-activating protein 7 (DLC1).	[58]

References

• [1] Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.J Transl Med. 2010 Sep 17;8:86. doi: 10.1186/1479-5876-8-86.
• [2] Aberrant DNA methylation of alternative promoter of DLC1 isoform 1 in meningiomas.J Neurooncol. 2016 Dec;130(3):473-484. doi: 10.1007/s11060-016-2261-3. Epub 2016 Sep 10.
• [3] Differentially expressed haptoglobin as a potential biomarker for type 2 diabetic mellitus in Hispanic population.Biofactors. 2017 May 6;43(3):424-433. doi: 10.1002/biof.1352. Epub 2017 Feb 20.
• [4] Overexpression of DLC-1 induces cell apoptosis and proliferation inhibition in the renal cell carcinoma.Cancer Lett. 2009 Sep 28;283(1):59-67. doi: 10.1016/j.canlet.2009.03.025. Epub 2009 Apr 19.
• [5] Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression.Biomed Res Int. 2013;2013:181384. doi: 10.1155/2013/181384. Epub 2012 Dec 23.
• [6] Haptoglobin gene expression in human glioblastoma cell lines.Neurosci Lett. 2001 May 11;303(3):181-4. doi: 10.1016/s0304-3940(01)01748-7.
• [7] DLC1 deficiency and YAP signaling drive endothelial cell contact inhibition of growth and tumorigenesis.Oncogene. 2019 Nov;38(45):7046-7059. doi: 10.1038/s41388-019-0944-x. Epub 2019 Aug 13.
• [8] Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome.Cell Rep. 2018 Sep 18;24(12):3115-3124. doi: 10.1016/j.celrep.2018.08.045.
• [9] Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011 Jun;25(6):1739-46. doi: 10.3892/or.2011.1239. Epub 2011 Mar 29.
• [10] circRNA-associated ceRNA network construction reveals the circRNAs involved in the progression and prognosis of breast cancer.J Cell Physiol. 2020 Apr;235(4):3973-3983. doi: 10.1002/jcp.29291. Epub 2019 Oct 15.
• [11] DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis.J Clin Invest. 2014 Apr;124(4):1646-59. doi: 10.1172/JCI71812. Epub 2014 Mar 3.
• [12] Aberrant gene promoter methylation of p16, FHIT, CRBP1, WWOX, and DLC-1 in Epstein-Barr virus-associated gastric carcinomas.Med Oncol. 2015 Apr;32(4):92. doi: 10.1007/s12032-015-0525-y. Epub 2015 Feb 27.
• [13] Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma.Epigenetics. 2016 Nov;11(11):780-790. doi: 10.1080/15592294.2016.1227899. Epub 2016 Sep 3.
• [14] Tumor suppressor DLC-1 induces apoptosis and inhibits the growth and invasion of colon cancer cells through the Wnt/-catenin signaling pathway.Oncol Rep. 2014 May;31(5):2270-8. doi: 10.3892/or.2014.3057. Epub 2014 Mar 5.
• [15] Expression of deleted in liver cancer 1 and plasminogen activator inhibitor 1 protein in ovarian carcinoma and their clinical significance.J Exp Clin Cancer Res. 2013 Aug 30;32(1):60. doi: 10.1186/1756-9966-32-60.
• [16] Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer.Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12492-7. doi: 10.1073/pnas.1507491112. Epub 2015 Sep 23.
• [17] DLC1 is unlikely to be a primary target for deletions on chromosome arm 8p22 in head and neck squamous cell carcinoma.Cancer Lett. 2004 Jun 25;209(2):207-13. doi: 10.1016/j.canlet.2003.12.018.
• [18] Analysis of serum Haptoglobin using glycoproteomics and lectin immunoassay in liver diseases in Hepatitis B virus infection.Clin Chim Acta. 2019 Aug;495:309-317. doi: 10.1016/j.cca.2019.04.072. Epub 2019 Apr 20.
• [19] Deleted in Liver Cancer 2 (DLC2) protein expression in hepatocellular carcinoma.Eur J Histochem. 2019 Feb 18;63(1):2981. doi: 10.4081/ejh.2019.2981.
• [20] DLC1 is the principal biologically-relevant down-regulated DLC family member in several cancers.Oncotarget. 2016 Jul 19;7(29):45144-45157. doi: 10.18632/oncotarget.9266.
• [21] Inactivation of the Dlc1 gene cooperates with downregulation of p15INK4b and p16Ink4a, leading to neoplastic transformation and poor prognosis in human cancer.Cancer Res. 2012 Nov 15;72(22):5900-11. doi: 10.1158/0008-5472.CAN-12-2368. Epub 2012 Sep 25.
• [22] Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer.Oncotarget. 2017 Oct 24;8(55):94834-94849. doi: 10.18632/oncotarget.22014. eCollection 2017 Nov 7.
• [23] DLC-1 as a modulator of proliferation, apoptosis and migration in Burkitt's lymphoma cells.Mol Biol Rep. 2011 Mar;38(3):1915-20. doi: 10.1007/s11033-010-0311-z. Epub 2010 Oct 1.
• [24] DLC-1 tumor suppressor regulates CD105 expression on human non-small cell lung carcinoma cells through inhibiting TGF-1 signaling.Exp Cell Res. 2020 Jan 15;386(2):111732. doi: 10.1016/j.yexcr.2019.111732. Epub 2019 Nov 23.
• [25] Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling. Oncogene. 2005 Mar 3;24(10):1774-87. doi: 10.1038/sj.onc.1207991.
• [26] DLC1 induces expression of E-cadherin in prostate cancer cells through Rho pathway and suppresses invasion.Oncogene. 2014 Feb 6;33(6):724-33. doi: 10.1038/onc.2013.7. Epub 2013 Feb 4.
• [27] Promoter hypermethylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers.Cancer Genet Cytogenet. 2003 Jan 15;140(2):113-7. doi: 10.1016/s0165-4608(02)00674-x.
• [28] Upregulation of DLC-1 inhibits pancreatic cancer progression: Studies with clinical samples and a pancreatic cancer model.Oncol Lett. 2019 Nov;18(5):5600-5606. doi: 10.3892/ol.2019.10871. Epub 2019 Sep 16.
• [29] A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.BMC Med Genet. 2013 Mar 20;14:36. doi: 10.1186/1471-2350-14-36.
• [30] Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis.Biochim Biophys Acta Mol Cell Res. 2018 Jan;1865(1):1-11. doi: 10.1016/j.bbamcr.2017.09.020. Epub 2017 Oct 3.
• [31] Overexpression of miR-301a-3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer-1 and runt-related transcription factor 3.J Cell Biochem. 2019 Apr;120(4):6078-6089. doi: 10.1002/jcb.27894. Epub 2018 Oct 25.
• [32] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [33] DLC1 tumor suppressor gene inhibits migration and invasion of multiple myeloma cells through RhoA GTPase pathway.Leukemia. 2009 Feb;23(2):383-90. doi: 10.1038/leu.2008.285. Epub 2008 Oct 16.
• [34] Genome-wide association study identifies five new schizophrenia loci.Nat Genet. 2011 Sep 18;43(10):969-76. doi: 10.1038/ng.940.
• [35] 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.
• [36] 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.
• [37] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [38] 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.
• [39] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [40] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [41] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [42] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [43] [Hypermethylation of CpG island of DLC-1 gene and arsenic trioxide-induced DLC-1 gene demethylation in multiple myeloma]. Zhonghua Yi Xue Za Zhi. 2014 Sep 30;94(36):2816-21.
• [44] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [45] 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.
• [46] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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] Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling. Oncogene. 2005 Mar 3;24(10):1774-87. doi: 10.1038/sj.onc.1207991.
• [49] 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.
• [50] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [51] Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007 Nov;31(11):1511-20.
• [52] Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011 Jun;25(6):1739-46. doi: 10.3892/or.2011.1239. Epub 2011 Mar 29.
• [53] 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.
• [54] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [55] 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.
• [56] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [57] 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.
• [58] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [59] 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.