FB2026_02 , released June 18, 2026
Human Disease Model Report: cancer, multiple, modulation by steroid hormone via mir-let7
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General Information
Name
cancer, multiple, modulation by steroid hormone via mir-let7
FlyBase ID
FBhh0000935
Disease Ontology Term
Parent Disease
OMIM
Overview

In two different Drosophila models of cancer assayed at the larval stage (see FBhh0000779 and FBhh0000772), it has been observed that tumorigenic cells are transformed into nontumorigenic cells after metamorphosis, and are eventually evicted from adult tissues. It has been shown that this process is dependent upon the increased ecdysone signalling that normally occurs during metamorphosis and into adulthood, and is mediated by the ecdysone-responsive microRNA mir-let7 and its target transcription factor gene chinmo. In these systems, reduction in the levels of either mir-let7 or chinmo results in persistence of tumorigenic cells and metastatic tumor growth in adults.

The human let7 microRNA family has been described as serving tumor suppressor functions, with downregulation observed in various cancers. There are at least 10 members of this family in human; several are encoded by multiple genes. There are also multiple microRNA genes in Drosophila categorized as within this family (as defined by shared 5' seed sequences).

Ecdysone (20-hydroxyecdysone) is the major steroid hormone in insects and plays essential roles in coordinating developmental transitions such as larval molting and metamorphosis; it is a member of a more general class called ecdysteroids. In Drosophila, ecdysone-regulated genes are bound by a heterodimer of ecdysone receptor (encoded by EcR) and Ultraspiracle (encoded by usp). In animals carrying a dominant-negative form of EcR, larval-derived tumorigenic cells continue to grow in adults and result in the accumulation of large tumors throughout the body; similar results are obtained in animals with RNAi-effected knockdown of usp.

[updated Dec. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: cancer, multiple, modulation by steroid hormone via mir-let7
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics

In human, 10 members of the let-7 family have been identified (Thammaiah and Jayaram, 2016 pubmed:30159414).

Cellular phenotype and pathology

The expression of let-7 family is required for developmental timing and tumor suppressor function; it must be suppressed for the self-renewal of stem cells (Lee et al., 2016; pubmed:26399619).

In various types of human cancer, downregulation of let-7 has been observed (Thammaiah and Jayaram, 2016 pubmed:30159414).

Molecular information

Higher animals have multiple isoforms of let-7 miRNAs encoded by multiple genes within the let-7 miRNA family; these isoforms share a consensus sequence called the 'seed sequence' (Lee et al., 2016; pubmed:26399619).

External links
Disease synonyms
cancer, multiple, let-7-related
cancer, multiple, modulation by steroid hormone via let-7
Search term: cancer, microRNA-related
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (4)
      Gene Snapshot
      Ecdysone receptor (EcR) encodes a protein that interacts with the product of usp to form the nuclear ecdysone receptor heterodimer, which modulates, in conjunction with co-activators and co-repressors, the activities of hundreds of genes in a tissue- and stage-specific way. EcR is widely expressed in embryonic and larval tissues and in some adult tissues where its activities (modulated by the hormone ecdysone) trigger both molting and metamorphosis. [Date last reviewed: 2019-03-07]
      Gene Groups / Pathways
      Comments on ortholog(s)

      Low- to moderate-scoring ortholog of human NR1H2, NR1H3, NR1H4 (1 Drosophila to 3 human). Dmel\EcR shares 33-38% identity and 47-55% 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
      Gene Groups / Pathways
      Comments on ortholog(s)
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Chronologically inappropriate morphogenesis (chinmo) encodes a putative BTB-zinc finger transcription factor. It is essential for neuronal temporal patterning. It also plays a role in the regulation of eye development, tumor formation, and the self-renewal and/or sexual identity of male somatic cyst stem cells by acting downstream of JAK-STAT signaling. [Date last reviewed: 2019-03-07]
      Molecular function (GO)
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        Encodes several isoforms of a BTB-zinc finger transcription factor with low levels of homology to several human ZBTB genes.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        5' seed sequence homologous to that of human let-7 microRNAs; several other Drosophila miRNAs have 5' seed sequence homologous to human let-7's, including mir-963, mir-977 and mir-984 (FBrf0242402).

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (146 groups)
          protein-protein
          Interacting group
          Assay
          References
          bimolecular fluorescence complementation, fluorescence microscopy
          fluorescent resonance energy transfer, fluorescence microscopy
          pull down, autoradiography, anti tag coimmunoprecipitation, anti tag western blot
          two hybrid, enzymatic study, western blot, anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot
          pull down, anti tag western blot
          anti bait coimmunoprecipitation, western blot, proximity-dependent biotin identification, Identification by mass spectrometry
          anti bait coimmunoprecipitation, western blot, two hybrid, Identification by mass spectrometry
          proximity ligation assay
          two hybrid, pull down, autoradiography
          anti bait coimmunoprecipitation, western blot, proximity-dependent biotin identification, Identification by mass spectrometry
          anti bait coimmunoprecipitation, western blot, proximity-dependent biotin identification, Identification by mass spectrometry
          two hybrid, pull down, autoradiography
          anti tag coimmunoprecipitation, anti tag western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti tag coimmunoprecipitation, western blot, pull down
          pull down, autoradiography
          anti tag coimmunoprecipitation, anti tag western blot
          two hybrid, pull down, autoradiography
          anti tag coimmunoprecipitation, anti tag western blot
          bimolecular fluorescence complementation
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          pull down, western blot, proximity ligation assay, fluorescence microscopy
          pull down, western blot
          anti tag coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          pull down, autoradiography, peptide massfingerprinting, anti bait coimmunoprecipitation, western blot
          pull down, western blot, anti tag coimmunoprecipitation
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry, two hybrid
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti tag coimmunoprecipitation, western blot
          pull down, autoradiography, two hybrid, anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot, molecular weight estimation by staining, proximity-dependent biotin identification, Identification by mass spectrometry, pull down, autoradiography
          proximity-dependent biotin identification, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot
          anti bait coimmunoprecipitation, western blot, proximity-dependent biotin identification, Identification by mass spectrometry
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, western blot
          proximity-dependent biotin identification, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot
          proximity-dependent biotin identification, Identification by mass spectrometry, anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, western blot
          anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, autoradiography
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry, two hybrid
          anti bait coimmunoprecipitation, western blot, proximity-dependent biotin identification, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, autoradiography
          anti tag coimmunoprecipitation, western blot, pull down, anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot
          two hybrid, pull down, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot, electrophoretic mobility shift assay, autoradiography, peptide massfingerprinting, experimental knowledge based, bimolecular fluorescence complementation, fluorescence microscopy, electrophoretic mobility supershift assay, x-ray crystallography
          pull down, autoradiography
          anti tag coimmunoprecipitation, western blot, pull down, autoradiography
          coimmunoprecipitation, western blot
          RNA-protein
          Interacting group
          Assay
          References
          electrophoretic mobility shift assay, autoradiography, systematic evolution of ligands by exponential enrichment, full identification by DNA sequencing
          RNA-RNA
          Interacting group
          Assay
          References
          fluorescence technology, luminiscence technology, necessary binding region, western blot, immunohistochemistry
          immunohistochemistry
          protein-protein
          Interacting group
          Assay
          References
          bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot, two hybrid
          pull down, anti tag western blot
          anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot
          two hybrid, pull down, autoradiography
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          two hybrid, pull down, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, anti tag coimmunoprecipitation, anti tag western blot, electrophoretic mobility shift assay, autoradiography, peptide massfingerprinting, experimental knowledge based, bimolecular fluorescence complementation, fluorescence microscopy, electrophoretic mobility supershift assay, x-ray crystallography
          pull down, autoradiography, two hybrid
          pull down, anti tag western blot, anti bait coimmunoprecipitation, western blot
          anti tag coimmunoprecipitation, anti tag western blot
          pull down, western blot, bimolecular fluorescence complementation, two hybrid
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          pull down, western blot
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          pull down, western blot, anti tag coimmunoprecipitation
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          two hybrid, pull down, autoradiography
          anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, autoradiography
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry
          two hybrid, anti tag coimmunoprecipitation, comigration in sds page, anti tag western blot
          pull down, autoradiography, anti bait coimmunoprecipitation, Identification by mass spectrometry
          anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, autoradiography
          RNA-protein
          Interacting group
          Assay
          References
          anti tag coimmunoprecipitation, primer specific pcr
          anti tag coimmunoprecipitation, full identification by RNA sequencing, anti bait coimmunoprecipitation, quantitative reverse transcription pcr
          pull down, western blot
          pull down, western blot
          protein-protein
          Interacting group
          Assay
          References
          two hybrid, molecular sieving
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, anti tag western blot
          array technology, two hybrid array
          RNA-protein
          Interacting group
          Assay
          References
          nucleic acid uv cross-linking assay, molecular weight estimation by staining, autoradiography, anti bait coimmunoprecipitation, northern blot, pull down, western blot
          enzymatic study, autoradiography, electrophoretic mobility shift assay, competition binding
          enzymatic study, autoradiography
          anti bait coimmunoprecipitation, quantitative reverse transcription pcr
          enzymatic study, autoradiography
          pull down, western blot
          RNA-RNA
          Interacting group
          Assay
          References
          immunohistochemistry, luminiscence technology
          luminiscence technology, necessary binding region, quantitative reverse transcription pcr
          western blot, luminiscence technology, necessary binding region
          immunohistochemistry, fluorescence technology, necessary binding region
          luminiscence technology, necessary binding region
          Alleles Reported to Model Human Disease (Disease Ontology) (14 alleles)
          Models Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 7 )
          Models Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Interaction
          References
          Models Based on Experimental Evidence ( 3 )
          Modifiers Based on Experimental Evidence ( 3 )
          Allele
          Disease
          Interaction
          References
          Models Based on Experimental Evidence ( 0 )
          Allele
          Disease
          Evidence
          References
          Modifiers Based on Experimental Evidence ( 3 )
          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
          RNAi constructs available
          Allele
          Transgene
          Publicly Available Stocks
          Selected Drosophila classical alleles
          Allele
          Allele class
          Mutagen
          Publicly Available Stocks
          amorphic allele - genetic evidence
          X ray
          P-element activity
          loss of function allele
          phiC31 integrase
          amorphic allele - genetic evidence
          loss of function allele
          ethyl methanesulfonate
          loss of function allele
          amorphic allele - genetic evidence
          Delta2-3 transposase
          amorphic allele - genetic evidence
          Delta2-3 transposase
          amorphic allele - genetic evidence
          Delta2-3 transposase
          loss of function allele
          amorphic allele - genetic evidence
          ethyl methanesulfonate
          loss of function allele
          CRISPR/Cas9
          amorphic allele - molecular evidence
          ends-out gene targeting
          References (5)