Human Disease Model Report: cancer, multiple, JAG-microRNA-related

General Information

Name

cancer, multiple, JAG-microRNA-related

FlyBase ID

FBhh0001039

Disease Ontology Term

carcinoma

Parent Disease

OMIM

Overview

In a genetic screen in Drosophila designed to identify genes that enhance or restrict Notch-induced tumorigenesis, the microRNA gene Dmel\mir-8 was identified as an inhibitor of Notch-induced overgrowth and tumor metastasis. Overexpression and loss-of-function mutations of mir-8 result in developmental defects similar to those observed with impaired Notch signalling. It was determined that mir-8 directly inhibits the translation of the Notch ligand Serrate (Ser) and that overexpression of Ser rescues the growth defect produced by mir-8 overexpression.

Extending these experiments to the orthologous genes in human, it was found that MIR200C and MIR141 directly inhibit JAGGED1. In a metastatic prostate cancer cell line, overexpression of the miRNAs decreased JAG1 protein levels and impeded cell growth.

[updated May 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, multiple, JAG-microRNA-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Notch signaling is an evolutionarily conserved intercellular signaling pathway that participates in critical processes throughout development, from embryogenesis to determination of adult stem cells. Activation of the Notch signaling pathway is observed in a number of cancers.

(FlyBase Curators, 2013-)

Genetics

Cellular phenotype and pathology

Molecular information

External links

Gene2Function (human gene): JAG1
Gene2Function (human gene): JAG2
Gene2Function (human gene): MIR200C microRNA 200c
Gene2Function (human gene): MIR141 microRNA 141
Gene Cards: MIR200C gene
Gene Cards: MIR141 gene
Gene Cards: JAG1
Gene Cards: JAG2
Gene Cards: MIR200C microRNA 200c
Gene Cards: MIR141 microRNA 141
MedlinePlus (gene): JAG1
MedlinePlus (gene): JAG2
MARRVEL (human gene): JAG1
MARRVEL (human gene): JAG2
MARRVEL (human gene): MIR200C microRNA 200c
MARRVEL (human gene): MIR141 microRNA 141
NCBI (Entrez) gene: MIR200C microRNA 200c
NCBI (Entrez) gene: MIR141 microRNA 141
NCBI (Entrez) gene: JAG1; jagged canonical Notch ligand 1
NCBI (Entrez) gene: JAG2; jagged canonical Notch ligand 2

Disease synonyms

Related Diseases

Related human health report(s)

cancer, multiple, epigenetic mechanisms

cancer, multiple, Notch signaling pathway

Ortholog Information

Human gene(s) in FlyBase

Hsap\JAG1

Human gene (HGNC)

Symbol / Name

JAG2; jagged canonical Notch ligand 2

D. melanogaster ortholog (based on DIOPT)

Dmel\Ser

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Human gene (HGNC)

Symbol / Name

JAG1; jagged canonical Notch ligand 1

D. melanogaster ortholog (based on DIOPT)

Dmel\Ser

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (2)

Dmel\Ser

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

NTCH-C
DSL

Comments on ortholog(s)

High-scoring ortholog of human JAG1 and JAG2 (1 Drosophila to 2 human). Dmel\Ser shares 33-35% identity and 46% similarity with the human genes.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\mir-8

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

RISC complex

Gene Groups / Pathways

Comments on ortholog(s)

Orthologous to human MIR200B, MIR200C, MIR141 and others (FBrf0242402).

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (50 groups)

Ser

RNA-RNA

Interacting group

Assay

References

Ser - mir-8

luminiscence technology, necessary binding region, fluorescence technology, immunohistochemistry

(Vallejo et al., 2011)

protein-protein

Interacting group

Assay

References

Ser - cno

anti tag coimmunoprecipitation, western blot

(Pérez-Gómez et al., 2013)

Ser - mib1

anti tag coimmunoprecipitation, anti tag western blot

(Seib et al., 2025, Lai et al., 2005)

Ser - N

affinity technology, fluorescence microscopy, inferred by author, bead aggregation assay, tag visualisation by alkaline phosphatase activity, anti bait coimmunoprecipitation, cross-linking study, western blot, anti tag coimmunoprecipitation, confocal microscopy, pull down, tag visualisation

(Pandey et al., 2019, Fleming et al., 2013, Pérez-Gómez et al., 2013, Yamamoto et al., 2012, Kim et al., 2010, Xu et al., 2007, Pérez et al., 2005, Wesley, 1999, Rebay et al., 1991)

Ser - neur

anti bait coimmunoprecipitation, western blot, anti tag western blot, anti tag coimmunoprecipitation

(Liu et al., 2012, Glittenberg et al., 2006, Pitsouli and Delidakis, 2005)

mir-8

RNA-protein

Interacting group

Assay

References

mir-8 - AGO1

anti bait coimmunoprecipitation, northern blot, pull down, western blot

(Kakumani et al., 2020, Lim et al., 2020)

mir-8 - AGO2

anti tag coimmunoprecipitation, northern blot

(Abe et al., 2014)

mir-8 - Dcr-1

enzymatic study, autoradiography

(Tsutsumi et al., 2011)

mir-8 - Fmr1

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Yang et al., 2009)

mir-8 - His1

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Liu et al., 2016)

mir-8 - loqs

fluorescence polarization spectroscopy, predetermined participant

(Tants et al., 2017)

mir-8 - Rox8

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Guo et al., 2020)

mir-8 - SmD1

anti bait coimmunoprecipitation, primer specific pcr

(Xiong et al., 2015)

mir-8 - SmD2

anti tag coimmunoprecipitation, primer specific pcr

(Xiong et al., 2015)

mir-8 - Unr

pull down, western blot

(Kakumani et al., 2020)

RNA-RNA

Interacting group

Assay

References

mir-8 - Adgf-A

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Adgf-B

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - ATP6AP2

luminiscence technology, quantitative reverse transcription pcr

(Lim et al., 2020)

mir-8 - caly

luminiscence technology

(Hyun et al., 2009)

mir-8 - Ced-12

luminiscence technology

(Hyun et al., 2009)

mir-8 - CG8420

quantitative reverse transcription pcr

(Karres et al., 2007)

mir-8 - CG13060

quantitative reverse transcription pcr

(Karres et al., 2007)

mir-8 - CG32767

luminiscence technology, necessary binding region

(Kennell et al., 2008)

mir-8 - Cpr56F

quantitative reverse transcription pcr

(Karres et al., 2007)

mir-8 - dbo

luminiscence technology

(Hyun et al., 2009)

mir-8 - dl

luminiscence technology, quantitative reverse transcription pcr

(Lee and Hyun, 2014)

mir-8 - ena

fluorescence technology, necessary binding region, immunohistochemistry

(Loya et al., 2014)

mir-8 - Gug

quantitative reverse transcription pcr, luminiscence technology, necessary binding region

(Karres et al., 2007)

mir-8 - Idgf1

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Idgf2

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Idgf3

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Idgf6

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Ilp6

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - ImpL2

quantitative reverse transcription pcr

(Lee et al., 2015)

mir-8 - Lap1

luminiscence technology

(Hyun et al., 2009)

mir-8 - Lar

luminiscence technology

(Nesler et al., 2013, Hyun et al., 2009)

mir-8 - pan

western blot

(Kennell et al., 2008)

mir-8 - pnut

immunohistochemistry

(Eichenlaub et al., 2016)

mir-8 - sd

fluorescence technology

(Sander et al., 2018)

mir-8 - Ser

luminiscence technology, necessary binding region, fluorescence technology, immunohistochemistry

(Vallejo et al., 2011)

mir-8 - spi

quantitative reverse transcription pcr, fluorescence technology, luminiscence technology, necessary binding region

(Morante et al., 2013)

mir-8 - Tl

luminiscence technology, quantitative reverse transcription pcr

(Lee and Hyun, 2014)

mir-8 - ush

luminiscence technology, western blot, quantitative reverse transcription pcr

(Lee and Hyun, 2014, Hyun et al., 2009)

mir-8 - Vha26

western blot, quantitative reverse transcription pcr, luminiscence technology

(Lim et al., 2020)

mir-8 - Vha55

luminiscence technology, quantitative reverse transcription pcr, western blot

(Lim et al., 2020)

mir-8 - Vha100-2

luminiscence technology, quantitative reverse transcription pcr

(Lim et al., 2020)

mir-8 - VhaAC45

luminiscence technology, quantitative reverse transcription pcr

(Lim et al., 2020)

mir-8 - Wdr37

luminiscence technology

(Hyun et al., 2009)

mir-8 - wg

luminiscence technology

(Nesler et al., 2013)

mir-8 - wls

immunohistochemistry, luminiscence technology, necessary binding region

(Kennell et al., 2008)

mir-8 - yki

fluorescence technology

(Sander et al., 2018)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

Ser

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

Ser^DN.UAS

model of dilated cardiomyopathy

CEA

(Kim et al., 2010)

Ser^RNAi.UAS.cUa

model of dilated cardiomyopathy

CEA

(Kim et al., 2010)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

Ser^RX82

ameliorates amyotrophic lateral sclerosis

modeled by Hsap\TARDBP^UAS.cHa, Delta^RevF10

(Zhan et al., 2013)

Ser¹

ameliorates Schimke immuno-osseous dysplasia

modeled by Marcal1^UAS.cBa

(Morimoto et al., 2016)

mir-8

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

mir-8^UAS.cUa

model of cancer

CEA with Egfr^UAS.cBa

(Eichenlaub et al., 2016)

Modifiers Based on Experimental Evidence ( 3 )

Allele

Disease

Interaction

References

mir-8^{UAS.DsRed(Unk)}

ameliorates high grade glioma

modeled by Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}, btl::Egfr^λ.UAS

(Jarabo et al., 2021)

mir-8^SC1

ameliorates cancer

modeled by lola^GS88A8, psq^GS88A8

(Vallejo et al., 2011)

mir-8^UAS.cVa

ameliorates cancer

modeled by lola^GS88A8, psq^GS88A8

(Vallejo et al., 2011)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

mir-8^{UAS.DsRed(Unk)}

P{UAS-DsRed-mir-8.L}

w^*; P{UAS-DsRed-mir-8.L}3/TM3, Sb¹

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

w¹¹¹⁸; P{GD14453}v27172

y¹ v¹; P{TRiP.JF03140}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01179}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Ser¹

spontaneous

P{NIG.11658R}3/TM3, P{ActGFP}JMR2, Ser¹

Ser^mf553

loss of function allele

minos activity

Ser^CS94

amorphic allele - genetic evidence

Ser^RX82

loss of function allele

X ray

Delta^RevF10 e^* Ser^RX82 P{neoFRT}82B/TM6B, Tb¹

Ser^RX107

loss of function allele

X ray

Ser^RX106

amorphic allele - genetic evidence

X ray

mwh¹ red¹ e¹ Ser^RX106/TM6B, Tb¹

Ser^rev2-11

loss of function allele

X ray

mir-8^Δ2

amorphic allele - molecular evidence

Delta2-3 transposase

w^*; mir-8^Δ2/CyO, P{GAL4-Kr.C}DC3, P{UAS-GFP.S65T}DC7

mir-8^SC1

mir-8^Δ

amorphic allele - molecular evidence

FLPase

References (6)

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