Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT393IMA)

• DOT Name: Transcription factor 21 (TCF21)
• Synonyms: TCF-21; Capsulin; Class A basic helix-loop-helix protein 23; bHLHa23; Epicardin; Podocyte-expressed 1; Pod-1
• Gene Name: TCF21
• Related Disease:
  Advanced cancer
  Acute myelogenous leukaemia
  Analgesia
  Bladder cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Carcinoma
  Carcinoma of esophagus
  Clear cell renal carcinoma
  Crohn disease
  Endometriosis
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Hyperglycemia
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung cancer
  Melanoma
  Non-small-cell lung cancer
  Obesity
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Squamous cell carcinoma
  Thrombophilia
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adrenal cortex neoplasm
  Adrenocortical carcinoma
  Lung carcinoma
  Stroke
  Urinary tract infection
  Arteriosclerosis
  Atherosclerosis
  Colorectal carcinoma
  Gastric cancer
  Hepatocellular carcinoma
  Kidney cancer
  Renal carcinoma
  Stomach cancer
• UniProt ID: TCF21_HUMAN
• Pfam ID: PF00010
• Sequence:
  MSTGSLSDVEDLQEVEMLECDGLKMDSNKEFVTSNESTEESSNCENGSPQKGRGGLGKRR
  KAPTKKSPLSGVSQEGKQVQRNAANARERARMRVLSKAFSRLKTTLPWVPPDTKLSKLDT
  LRLASSYIAHLRQILANDKYENGYIHPVNLTWPFMVAGKPESDLKEVVTASRLCGTTAS
• Function: Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis. May play a role in the specification or differentiation of one or more subsets of epicardial cell types.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Analgesia	DISK3TVI	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Posttranslational Modification	[4]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Posttranslational Modification	[8]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[9]
Endometriosis	DISX1AG8	Strong	Altered Expression	[10]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[11]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[7]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Posttranslational Modification	[12]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[13]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Lung cancer	DISCM4YA	Strong	Posttranslational Modification	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[16]
Obesity	DIS47Y1K	Strong	Altered Expression	[18]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[11]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Posttranslational Modification	[4]
Prostate carcinoma	DISMJPLE	Strong	Posttranslational Modification	[4]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Thrombophilia	DISQR7U7	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Posttranslational Modification	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Posttranslational Modification	[4]
Adrenal cortex neoplasm	DISO17X1	moderate	Altered Expression	[23]
Adrenocortical carcinoma	DISZF4HX	moderate	Altered Expression	[23]
Lung carcinoma	DISTR26C	moderate	Posttranslational Modification	[16]
Stroke	DISX6UHX	moderate	Genetic Variation	[24]
Urinary tract infection	DISMT6UV	moderate	Biomarker	[25]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[26]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[26]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[27]
Gastric cancer	DISXGOUK	Limited	Biomarker	[28]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[29]
Kidney cancer	DISBIPKM	Limited	Altered Expression	[8]
Renal carcinoma	DISER9XT	Limited	Altered Expression	[8]
Stomach cancer	DISKIJSX	Limited	Biomarker	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transcription factor 21 (TCF21).	[30]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Transcription factor 21 (TCF21).	[31]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor 21 (TCF21).	[32]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Transcription factor 21 (TCF21).	[33]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Transcription factor 21 (TCF21).	[34]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Transcription factor 21 (TCF21).	[35]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transcription factor 21 (TCF21).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transcription factor 21 (TCF21).	[37]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Transcription factor 21 (TCF21).	[40]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor 21 (TCF21).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transcription factor 21 (TCF21).	[39]

References

• [1] TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.Front Endocrinol (Lausanne). 2018 Feb 22;9:38. doi: 10.3389/fendo.2018.00038. eCollection 2018.
• [2] Promoter methylation of the candidate tumor suppressor gene TCF21 in myelodysplastic syndrome and acute myeloid leukemia.Am J Transl Res. 2019 Jun 15;11(6):3450-3460. eCollection 2019.
• [3] Impact of epidural analgesia on the systemic biomarker response after hepatic resection.Oncotarget. 2019 Jan 15;10(5):584-594. doi: 10.18632/oncotarget.26549. eCollection 2019 Jan 15.
• [4] TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a simultaneous detection of urological cancers.Epigenetics. 2011 Sep 1;6(9):1120-30. doi: 10.4161/epi.6.9.16376. Epub 2011 Sep 1.
• [5] Role of microRNA-92a in metastasis of osteosarcoma cells in vivo and in vitro by inhibiting expression of TCF21 with the transmission of bone marrow derived mesenchymal stem cells.Cancer Cell Int. 2019 Feb 12;19:31. doi: 10.1186/s12935-019-0741-1. eCollection 2019.
• [6] TCF21 genetic polymorphisms and breast cancer risk in Chinese women.Oncotarget. 2016 Aug 23;7(34):55757-55764. doi: 10.18632/oncotarget.9825.
• [7] Expression of Transcription Factor 21 (TCF21) and Upregulation Its Level Inhibits Invasion and Metastasis in Esophageal Squamous Cell Carcinoma.Med Sci Monit. 2018 Jun 17;24:4128-4136. doi: 10.12659/MSM.909138.
• [8] TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration.Mol Oncol. 2018 Feb;12(2):166-179. doi: 10.1002/1878-0261.12149. Epub 2017 Dec 14.
• [9] Postoperative Interleukin-6 Predicts Intra-abdominal Septic Complications at an Early Stage After Elective Intestinal Operation for Crohn's Disease Patients.Inflamm Bowel Dis. 2018 Aug 16;24(9):1992-2000. doi: 10.1093/ibd/izy090.
• [10] Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis.Am J Pathol. 2020 Jan;190(1):145-157. doi: 10.1016/j.ajpath.2019.09.008. Epub 2019 Oct 11.
• [11] Clinical Stratification of High-Grade Ovarian Serous Carcinoma Using a Panel of Six Biomarkers.J Clin Med. 2019 Mar 8;8(3):330. doi: 10.3390/jcm8030330.
• [12] Protein expression and promoter methylation of the candidate biomarker TCF21 in head and neck squamous cell carcinoma.Cell Oncol (Dordr). 2013 Jun;36(3):213-24. doi: 10.1007/s13402-013-0129-5. Epub 2013 Mar 26.
• [13] Optimal Timing of Glucose Measurements After Total Joint Arthroplasty.J Arthroplasty. 2019 Jul;34(7S):S152-S158. doi: 10.1016/j.arth.2019.01.004. Epub 2019 Jan 9.
• [14] Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.PLoS Genet. 2015 May 28;11(5):e1005202. doi: 10.1371/journal.pgen.1005202. eCollection 2015 May.
• [15] Prognostic significance of TCF21 mRNA expression in patients with lung adenocarcinoma.Sci Rep. 2017 May 17;7(1):2027. doi: 10.1038/s41598-017-02290-2.
• [16] Promoter methylation of TCF21 may repress autophagy in the progression of lung cancer.J Cell Commun Signal. 2018 Jun;12(2):423-432. doi: 10.1007/s12079-017-0418-2. Epub 2017 Oct 30.
• [17] Epigenetic deregulation of TCF21 inhibits metastasis suppressor KISS1 in metastatic melanoma.Carcinogenesis. 2011 Oct;32(10):1467-73. doi: 10.1093/carcin/bgr138. Epub 2011 Jul 18.
• [18] Increased Ifi202b/IFI16 expression stimulates adipogenesis in mice and humans.Diabetologia. 2018 May;61(5):1167-1179. doi: 10.1007/s00125-018-4571-9. Epub 2018 Feb 24.
• [19] Functional balance between Tcf21-Slug defines cellular plasticity and migratory modalities in high grade serous ovarian cancer cell lines.Carcinogenesis. 2020 Jun 17;41(4):515-526. doi: 10.1093/carcin/bgz119.
• [20] miR-21 downregulated TCF21 to inhibit KISS1 in renal cancer.Urology. 2012 Dec;80(6):1298-302.e1. doi: 10.1016/j.urology.2012.08.013.
• [21] Dysregulation of -catenin, WISP1 and TCF21 predicts disease-specific survival and primary response against radio(chemo)therapy in patients with locally advanced squamous cell carcinomas of the head and neck.Clin Otolaryngol. 2019 May;44(3):263-272. doi: 10.1111/coa.13281. Epub 2019 Feb 5.
• [22] Ability of Thromboelastography to Detect Hypercoagulability: A Systematic Review and Meta-Analysis.J Orthop Trauma. 2020 Jun;34(6):278-286. doi: 10.1097/BOT.0000000000001714.
• [23] New evidences on the regulation of SF-1 expression by POD1/TCF21 in adrenocortical tumor cells.Clinics (Sao Paulo). 2017 Jun;72(6):391-394. doi: 10.6061/clinics/2017(06)10.
• [24] Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.Stroke. 2014 Jan;45(1):24-36. doi: 10.1161/STROKEAHA.113.002707. Epub 2013 Nov 21.
• [25] Outcomes of Early Removal of Urinary Catheter Following Rectal Resection for Cancer.Ann Surg Oncol. 2019 Jan;26(1):79-85. doi: 10.1245/s10434-018-6822-x. Epub 2018 Oct 23.
• [26] MicroRNA-30-3p Suppresses Inflammatory Factor-Induced Endothelial Cell Injury by Targeting TCF21.Mediators Inflamm. 2019 Jul 2;2019:1342190. doi: 10.1155/2019/1342190. eCollection 2019.
• [27] Natural Killer Cell IFN Secretion is Profoundly Suppressed Following Colorectal Cancer Surgery.Ann Surg Oncol. 2018 Nov;25(12):3747-3754. doi: 10.1245/s10434-018-6691-3. Epub 2018 Sep 5.
• [28] Safety of early oral feeding after total laparoscopic radical gastrectomy for gastric cancer (SOFTLY): Study protocol for a randomized controlled trial.Trials. 2019 Jun 26;20(1):384. doi: 10.1186/s13063-019-3493-2.
• [29] Expression tendency and prognostic value of TCF21 in hepatocellular carcinoma.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1466-1470. doi: 10.1080/21691401.2019.1601102.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [34] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [35] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [36] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [37] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [38] 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.
• [39] 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.
• [40] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.