Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGB7EBG)

• DOT Name: Ras association domain-containing protein 10 (RASSF10)
• Gene Name: RASSF10
• Related Disease:
  Acute lymphocytic leukaemia
  Breast cancer
  Breast carcinoma
  Astrocytoma
  Benign prostatic hyperplasia
  Carcinoma of esophagus
  Childhood acute lymphoblastic leukemia
  Colorectal carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Leukemia
  Neoplasm
  Neoplasm of esophagus
  Prostate carcinoma
  Stomach cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Lung cancer
  Lung carcinoma
  Thyroid gland papillary carcinoma
  Cutaneous melanoma
  Melanoma
  Neuroblastoma
• UniProt ID: RASFA_HUMAN
• Pfam ID: PF21712
• Sequence:
  MDPSEKKISVWICQEEKLVSGLSRRTTCSDVVRVLLEDGCRRRRRQRRSRRLGSAGDPHG
  PGELPEPPNEDDEDDDEALPQGMLCGPPQCYCIVEKWRGFERILPNKTRILRLWAAWGEE
  QENVRFVLVRSEASLPNAGPRSAEARVVLSRERPCPARGAPARPSLAMTQEKQRRVVRKA
  FRKLAKLNRRRQQQTPSSCSSTSSSTASSCSSSPRTHESASVERMETLVHLVLSQDHTIR
  QQVQRLHELDREIDHYEAKVHLDRMRRHGVNYVQDTYLVGAGIELDGSRPGEEPEEVAAE
  AEEAAAAPPLAGEAQAAALEELARRCDDLLRLQEQRVQQEELLERLSAEIQEELNQRWMR
  RRQEELAAREEPLEPDGGPDGELLLEQERVRTQLSTSLYIGLRLNTDLEAVKSDLDYSQQ
  QWDSKKRELQGLLQTLHTLELTVAPDGAPGSGSPSREPGPQACADMWVDQARGLAKSGPG
  NDEDSDTGLSSMHSQDSDSLPMCESLV
• Function: Plays an important role in regulating embryonic neurogenesis.
• Tissue Specificity: Expressed in brain. Tends to be down-regulated in astrocytic gliomas due to promoter methylation. Methylation occurs early in gliomagenesis and the extent of methylation parallels with higher glioma grades, so that methylation is observed in close to 70% WHO grade IV primary glioblastomas, but not in grade I astrocytomas.

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Definitive	Posttranslational Modification	[2]
Breast carcinoma	DIS2UE88	Definitive	Posttranslational Modification	[2]
Astrocytoma	DISL3V18	Strong	Posttranslational Modification	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[5]
Gastric cancer	DISXGOUK	Strong	Posttranslational Modification	[7]
Glioblastoma multiforme	DISK8246	Strong	Posttranslational Modification	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[8]
Leukemia	DISNAKFL	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[10]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[4]
Stomach cancer	DISKIJSX	Strong	Posttranslational Modification	[7]
Thyroid cancer	DIS3VLDH	Strong	Posttranslational Modification	[11]
Thyroid gland carcinoma	DISMNGZ0	Strong	Posttranslational Modification	[11]
Thyroid tumor	DISLVKMD	Strong	Posttranslational Modification	[11]
Lung cancer	DISCM4YA	Disputed	Altered Expression	[12]
Lung carcinoma	DISTR26C	Disputed	Altered Expression	[12]
Thyroid gland papillary carcinoma	DIS48YMM	Disputed	Altered Expression	[13]
Cutaneous melanoma	DIS3MMH9	Limited	Posttranslational Modification	[14]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[17]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ras association domain-containing protein 10 (RASSF10).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ras association domain-containing protein 10 (RASSF10).	[21]

1 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 affects the methylation of Ras association domain-containing protein 10 (RASSF10).	[19]

References

• [1] Residual methylation of tumor suppressor gene promoters, RASSF6 and RASSF10, as novel biomarkers for minimal residual disease detection in adult acute lymphoblastic leukemia.Ann Hematol. 2019 Dec;98(12):2719-2727. doi: 10.1007/s00277-019-03775-y. Epub 2019 Sep 5.
• [2] Methylation of RASSF10 promotes cell proliferation and serves as a docetaxel resistant marker in human breast cancer.Discov Med. 2015 Nov;20(111):261-71.
• [3] Epigenetic inactivation of the RASSF10 candidate tumor suppressor gene is a frequent and an early event in gliomagenesis.Oncogene. 2011 Feb 24;30(8):978-89. doi: 10.1038/onc.2010.471. Epub 2010 Oct 18.
• [4] Epigenetic down regulation of RASSF10 and its possible clinical implication in prostate carcinoma.Prostate. 2012 Oct 1;72(14):1550-8. doi: 10.1002/pros.22510. Epub 2012 Mar 13.
• [5] Epigenetic silencing of RASSF10 promotes tumor growth in esophageal squamous cell carcinoma.Discov Med. 2014 Apr;17(94):169-78.
• [6] Low expression of RASSF10 is associated with poor survival in patients with colorectal cancer.Hum Pathol. 2017 Apr;62:108-114. doi: 10.1016/j.humpath.2016.12.016. Epub 2016 Dec 30.
• [7] The value of serum RASSF10 hypermethylation as a diagnostic and prognostic tool for gastric cancer.Tumour Biol. 2016 Aug;37(8):11249-57. doi: 10.1007/s13277-016-5001-6. Epub 2016 Mar 5.
• [8] Study on the relationship between the RASSF10 gene and the biological behavior of hepatocellular carcinoma cells.Eur Rev Med Pharmacol Sci. 2017 Aug;21(16):3576-3580.
• [9] The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias.Mol Cancer. 2009 Jul 1;8:42. doi: 10.1186/1476-4598-8-42.
• [10] RASSF10 Is a TGF-Target That Regulates ASPP2 and E-Cadherin Expression and Acts as Tumor Suppressor That Is Epigenetically Downregulated in Advanced Cancer.Cancers (Basel). 2019 Dec 8;11(12):1976. doi: 10.3390/cancers11121976.
• [11] Frequent epigenetic inactivation of RASSF10 in thyroid cancer.Epigenetics. 2009 Nov 16;4(8):571-6. doi: 10.4161/epi.4.8.10056. Epub 2009 Nov 14.
• [12] RASSF10 suppresses lung cancer proliferation and invasion by decreasing the level of phosphorylated LRP6.Mol Carcinog. 2019 Jul;58(7):1168-1180. doi: 10.1002/mc.23000. Epub 2019 Mar 4.
• [13] RASSF10 is Epigenetically Inactivated and Suppresses Cell Proliferation and Induces Cell Apoptosis by Activating the p53 Signalling Pathway in Papillary Thyroid Carcinoma Cancer.Cell Physiol Biochem. 2017;41(3):1229-1239. doi: 10.1159/000464386. Epub 2017 Mar 7.
• [14] RASSF10 promoter hypermethylation is frequent in malignant melanoma of the skin but uncommon in nevus cell nevi.J Invest Dermatol. 2012 Mar;132(3 Pt 1):687-94. doi: 10.1038/jid.2011.380. Epub 2011 Nov 24.
• [15] The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma.Mol Cancer. 2012 Jun 13;11:40. doi: 10.1186/1476-4598-11-40.
• [16] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [17] 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.
• [18] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [19] 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.
• [20] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [21] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.