Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVWP0FN)

DOT Name Protein lin-28 homolog B (LIN28B)
Synonyms Lin-28B
Gene Name LIN28B
Related Disease
Atypical teratoid/rhabdoid tumour ( )
Matthew-Wood syndrome ( )
Medulloblastoma ( )
Melanoma ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Alzheimer disease ( )
Benign neoplasm ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Childhood kidney Wilms tumor ( )
Colon cancer ( )
Colon carcinoma ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Liver cancer ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Major depressive disorder ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Precocious puberty ( )
Prostate cancer ( )
Prostate carcinoma ( )
Schizophrenia ( )
Squamous cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Wilms tumor ( )
Gastric cancer ( )
Plasma cell myeloma ( )
Stomach cancer ( )
Type-1/2 diabetes ( )
leukaemia ( )
Leukemia ( )
Neuroblastoma ( )
Colorectal carcinoma ( )
Malignant soft tissue neoplasm ( )
Metastatic malignant neoplasm ( )
Sarcoma ( )
UniProt ID
LN28B_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
4A4I
Pfam ID
PF00313 ; PF00098
Sequence
MAEGGASKGGGEEPGKLPEPAEEESQVLRGTGHCKWFNVRMGFGFISMINREGSPLDIPV
DVFVHQSKLFMEGFRSLKEGEPVEFTFKKSSKGLESIRVTGPGGSPCLGSERRPKGKTLQ
KRKPKGDRCYNCGGLDHHAKECSLPPQPKKCHYCQSIMHMVANCPHKNVAQPPASSQGRQ
EAESQPCTSTLPREVGGGHGCTSPPFPQEARAEISERSGRSPQEASSTKSSIAPEEQSKK
GPSVQKRKKT
Function
Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA. Does not act on pri-miR21. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation. This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent. Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression. When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.
Tissue Specificity
Expressed at high levels in the placenta and, at mucher lower, in testis and fetal liver . Isoform 1 is only detected in placenta and in moderately and poorly differentiated hepatocellular carcinoma cells (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Tends to be up-regulated in triple-negative (ER-,PR-,HER2-) breast tumors, as well as in liver, ovarian, and thyroid carcinomas .

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Atypical teratoid/rhabdoid tumour DIS1FA0D Definitive Altered Expression [1]
Matthew-Wood syndrome DISA7HR7 Definitive Biomarker [2]
Medulloblastoma DISZD2ZL Definitive Altered Expression [1]
Melanoma DIS1RRCY Definitive Altered Expression [3]
Acute monocytic leukemia DIS28NEL Strong Biomarker [4]
Acute myelogenous leukaemia DISCSPTN Strong Altered Expression [4]
Alzheimer disease DISF8S70 Strong Biomarker [5]
Benign neoplasm DISDUXAD Strong Biomarker [6]
Bladder cancer DISUHNM0 Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Altered Expression [9]
Childhood kidney Wilms tumor DIS0NMK3 Strong Genetic Variation [10]
Colon cancer DISVC52G Strong Altered Expression [11]
Colon carcinoma DISJYKUO Strong Altered Expression [11]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [12]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [13]
Liver cancer DISDE4BI Strong Biomarker [14]
Lung adenocarcinoma DISD51WR Strong Biomarker [15]
Lung cancer DISCM4YA Strong Biomarker [16]
Lung carcinoma DISTR26C Strong Biomarker [16]
Lung neoplasm DISVARNB Strong Altered Expression [16]
Major depressive disorder DIS4CL3X Strong Biomarker [17]
Neoplasm DISZKGEW Strong Biomarker [8]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [18]
Ovarian cancer DISZJHAP Strong Biomarker [19]
Ovarian neoplasm DISEAFTY Strong Biomarker [19]
Precocious puberty DISYI2XZ Strong Genetic Variation [20]
Prostate cancer DISF190Y Strong Altered Expression [21]
Prostate carcinoma DISMJPLE Strong Altered Expression [21]
Schizophrenia DISSRV2N Strong Genetic Variation [22]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [23]
Urinary bladder cancer DISDV4T7 Strong Biomarker [7]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [7]
Wilms tumor DISB6T16 Strong Genetic Variation [10]
Gastric cancer DISXGOUK moderate Biomarker [24]
Plasma cell myeloma DIS0DFZ0 moderate Biomarker [25]
Stomach cancer DISKIJSX moderate Biomarker [24]
Type-1/2 diabetes DISIUHAP moderate Biomarker [26]
leukaemia DISS7D1V Disputed Biomarker [27]
Leukemia DISNAKFL Disputed Biomarker [27]
Neuroblastoma DISVZBI4 Disputed Altered Expression [28]
Colorectal carcinoma DIS5PYL0 Limited Biomarker [29]
Malignant soft tissue neoplasm DISTC6NO Limited Biomarker [30]
Metastatic malignant neoplasm DIS86UK6 Limited Biomarker [31]
Sarcoma DISZDG3U Limited Biomarker [30]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 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 Protein lin-28 homolog B (LIN28B). [32]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Protein lin-28 homolog B (LIN28B). [34]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Protein lin-28 homolog B (LIN28B). [35]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Protein lin-28 homolog B (LIN28B). [36]
Malathion DMXZ84M Approved Malathion increases the expression of Protein lin-28 homolog B (LIN28B). [37]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Protein lin-28 homolog B (LIN28B). [36]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Protein lin-28 homolog B (LIN28B). [39]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein lin-28 homolog B (LIN28B). [41]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Protein lin-28 homolog B (LIN28B). [42]
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⏷ Show the Full List of 9 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Protein lin-28 homolog B (LIN28B). [33]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Protein lin-28 homolog B (LIN28B). [38]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Protein lin-28 homolog B (LIN28B). [40]
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References

1 Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum.Cerebellum. 2017 Feb;16(1):122-131. doi: 10.1007/s12311-016-0774-0.
2 TGF- induces miR-100 and miR-125b but blocks let-7a through LIN28B controlling PDAC progression.Nat Commun. 2018 May 10;9(1):1845. doi: 10.1038/s41467-018-03962-x.
3 Carbon ion irradiation abrogates Lin28B-induced X-ray resistance in melanoma cells.J Radiat Res. 2017 Nov 1;58(6):765-771. doi: 10.1093/jrr/rrx022.
4 LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell-like Transcriptional Program in AML.Mol Cancer Res. 2017 Mar;15(3):294-303. doi: 10.1158/1541-7786.MCR-16-0275-T. Epub 2016 Dec 23.
5 Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2.J Cell Physiol. 2019 Dec;234(12):21860-21876. doi: 10.1002/jcp.28750. Epub 2019 May 8.
6 Lin28 promotes transformation and is associated with advanced human malignancies.Nat Genet. 2009 Jul;41(7):843-8. doi: 10.1038/ng.392. Epub 2009 May 31.
7 MacroH2A1 downregulation enhances the stem-like properties of bladder cancer cells by transactivation of Lin28B.Oncogene. 2016 Mar 10;35(10):1292-301. doi: 10.1038/onc.2015.187. Epub 2015 Jun 1.
8 Targeting LIN28B reprograms tumor glucose metabolism and acidic microenvironment to suppress cancer stemness and metastasis.Oncogene. 2019 Jun;38(23):4527-4539. doi: 10.1038/s41388-019-0735-4. Epub 2019 Feb 11.
9 Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms.Cell. 2011 Nov 23;147(5):1066-79. doi: 10.1016/j.cell.2011.10.039.
10 The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children.J Clin Lab Anal. 2018 Jan;32(1):e22200. doi: 10.1002/jcla.22200. Epub 2017 Mar 16.
11 LIN28B promotes the progression of colon cancer by increasing B-cell lymphoma 2 expression.Biomed Pharmacother. 2018 Jul;103:355-361. doi: 10.1016/j.biopha.2018.04.002. Epub 2018 Apr 24.
12 RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells.Signal Transduct Target Ther. 2018 Aug 31;3:23. doi: 10.1038/s41392-018-0026-5. eCollection 2018.
13 Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma.J Cancer. 2019 Oct 15;10(24):6074-6087. doi: 10.7150/jca.33421. eCollection 2019.
14 Dynamics and predicted drug response of a gene network linking dedifferentiation with beta-catenin dysfunction in hepatocellular carcinoma.J Hepatol. 2019 Aug;71(2):323-332. doi: 10.1016/j.jhep.2019.03.024. Epub 2019 Apr 4.
15 A cancer-testis non-coding RNA LIN28B-AS1 activates driver gene LIN28B by interacting with IGF2BP1 in lung adenocarcinoma.Oncogene. 2019 Mar;38(10):1611-1624. doi: 10.1038/s41388-018-0548-x. Epub 2018 Oct 23.
16 MiR-563 restrains cell proliferation via targeting LIN28B in human lung cancer.Thorac Cancer. 2020 Jan;11(1):55-61. doi: 10.1111/1759-7714.13257. Epub 2019 Nov 25.
17 Molecular and Functional Sex Differences of Noradrenergic Neurons in the Mouse Locus Coeruleus.Cell Rep. 2018 May 22;23(8):2225-2235. doi: 10.1016/j.celrep.2018.04.054.
18 MicroRNA?500 suppresses tumor progression in nonsmall cell lung cancer by regulating STAT3.Mol Med Rep. 2019 Dec;20(6):4973-4983. doi: 10.3892/mmr.2019.10737. Epub 2019 Oct 11.
19 Overexpression of the RNA-binding proteins Lin28B and IGF2BP3 (IMP3) is associated with chemoresistance and poor disease outcome in ovarian cancer.Br J Cancer. 2015 Jul 28;113(3):414-24. doi: 10.1038/bjc.2015.254. Epub 2015 Jul 9.
20 Association between MKRN3 and LIN28B polymorphisms and precocious puberty.BMC Genet. 2018 Jul 27;19(1):47. doi: 10.1186/s12863-018-0658-z.
21 Role of BioResponse 3,3'-Diindolylmethane in the Treatment of Human Prostate Cancer: Clinical Experience.Med Princ Pract. 2016;25 Suppl 2(Suppl 2):11-7. doi: 10.1159/000439307. Epub 2015 Oct 27.
22 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
23 Elevated Lin28B expression is correlated with lymph node metastasis in oral squamous cell carcinomas.J Oral Pathol Med. 2015 Nov;44(10):823-30. doi: 10.1111/jop.12314. Epub 2015 Feb 27.
24 RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1.Biomed Pharmacother. 2018 Aug;104:383-389. doi: 10.1016/j.biopha.2018.05.064. Epub 2018 May 25.
25 The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma.Leukemia. 2017 Apr;31(4):853-860. doi: 10.1038/leu.2016.296. Epub 2016 Oct 24.
26 The Lin28/let-7 axis regulates glucose metabolism.Cell. 2011 Sep 30;147(1):81-94. doi: 10.1016/j.cell.2011.08.033.
27 Inhibition of LIN28B impairs leukemia cell growth and metabolism in acute myeloid leukemia.J Hematol Oncol. 2017 Jul 11;10(1):138. doi: 10.1186/s13045-017-0507-y.
28 LIN28B increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors.Cell Death Differ. 2020 Apr;27(4):1225-1242. doi: 10.1038/s41418-019-0425-3. Epub 2019 Oct 10.
29 LIN28B/IRS1 axis is targeted by miR-30a-5p and promotes tumor growth in colorectal cancer.J Cell Biochem. 2020 Aug;121(8-9):3720-3729. doi: 10.1002/jcb.29529. Epub 2019 Nov 12.
30 Neoplastic Transformation of Human Mesenchymal Stromal Cells Mediated via LIN28B.Sci Rep. 2019 May 30;9(1):8101. doi: 10.1038/s41598-019-44536-1.
31 Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer.J Cancer. 2019 Jul 23;10(18):4397-4407. doi: 10.7150/jca.27590. eCollection 2019.
32 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
33 Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
34 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.
35 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
36 The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
37 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.
38 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
39 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.
40 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.
41 Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
42 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.