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  1. Article ; Online: A Roadmap for the Computational Prediction and Experimental Validation of Competitive Endogenous RNAs.

    Karreth, Florian A

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1970, Page(s) 237–250

    Abstract: MicroRNAs (miRNAs) are fine-tuners of gene expression and contribute to the regulation of most, if not all, biological processes in eukaryotes by targeting both coding and noncoding RNAs. Typically, miRNAs repress numerous target transcripts and most ... ...

    Abstract MicroRNAs (miRNAs) are fine-tuners of gene expression and contribute to the regulation of most, if not all, biological processes in eukaryotes by targeting both coding and noncoding RNAs. Typically, miRNAs repress numerous target transcripts and most target RNAs harbor binding sites for multiple miRNA families. It was recently proposed that transcripts sequester miRNAs and thereby regulate the abundance of other transcripts with which they have miRNA binding sites in common. Since competition for shared miRNAs is the mechanistic basis for this cross-regulation, such transcripts were termed competitive endogenous RNAs (ceRNAs). In this chapter, I discuss considerations for the computational prediction of ceRNAs based on miRNA binding site overlap. Moreover, I provide a framework for the experimental validation of miRNA-dependent reciprocal regulation of putative ceRNAs.
    MeSH term(s) Computational Biology/methods ; Gene Expression Regulation ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Software
    Chemical Substances MicroRNAs ; RNA, Long Noncoding ; RNA, Messenger
    Language English
    Publishing date 2019-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9207-2_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pseudogenes as Competitive Endogenous RNAs: Testing miRNA Dependency.

    Xu, Xiaonan / Karreth, Florian A

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2324, Page(s) 131–147

    Abstract: Pseudogenes may function as competitive endogenous RNAs (ceRNAs), where they regulate the expression of genes by sequestering shared miRNAs. ceRNAs are becoming more extensively identified and studied, and demonstrating the dependence of their effects on ...

    Abstract Pseudogenes may function as competitive endogenous RNAs (ceRNAs), where they regulate the expression of genes by sequestering shared miRNAs. ceRNAs are becoming more extensively identified and studied, and demonstrating the dependence of their effects on miRNA sequestration is critical to establish them as ceRNAs. Here, we outline an experimental approach to assess the miRNA dependency of a candidate pseudogene ceRNA.
    MeSH term(s) Animals ; Cell Line ; Cross-Linking Reagents ; Genes, Reporter/genetics ; Humans ; Luciferases/genetics ; Luciferases/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mutation ; Polymerase Chain Reaction ; Pseudogenes/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Regulatory Sequences, Ribonucleic Acid/genetics ; Transcription, Genetic ; Transfection
    Chemical Substances Cross-Linking Reagents ; MicroRNAs ; RNA, Messenger ; Regulatory Sequences, Ribonucleic Acid ; Luciferases (EC 1.13.12.-)
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1503-4_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Strategies to Study the Functions of Pseudogenes in Mouse Models of Cancer.

    Bok, Ilah / Karreth, Florian A

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2324, Page(s) 287–304

    Abstract: Aberrant expression of pseudogenes has been observed in many cancer types. Deregulated pseudogenes engage in a multitude of biological processes at the DNA, RNA, and protein levels and eventually facilitate disease progression. To investigate pseudogene ... ...

    Abstract Aberrant expression of pseudogenes has been observed in many cancer types. Deregulated pseudogenes engage in a multitude of biological processes at the DNA, RNA, and protein levels and eventually facilitate disease progression. To investigate pseudogene functions in cancer, cell lines and cell line transplantation models have been widely used. However, cancer biology is best studied in the context of an intact organism. Here, we present various strategies to investigate pseudogenes in genetically engineered mouse models and discuss advantages and disadvantages of the different approaches.
    MeSH term(s) Animals ; Cell Line, Tumor ; Drug Resistance, Microbial/genetics ; Embryonic Stem Cells ; Gene Expression Regulation ; Genes, Synthetic ; Heterografts ; Humans ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Neoplasm Transplantation ; Neoplasms, Experimental/genetics ; Promoter Regions, Genetic ; Pseudogenes/genetics ; RNA Interference ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Species Specificity ; Tetracycline/pharmacology ; Up-Regulation
    Chemical Substances Recombinant Proteins ; Tetracycline (F8VB5M810T)
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1503-4_18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Editorial: Structural and Functional Characterization of Circular RNAs.

    Grammatikakis, Ioannis / Karreth, Florian A / Panda, Amaresh C

    Frontiers in molecular biosciences

    2021  Volume 8, Page(s) 795286

    Language English
    Publishing date 2021-11-02
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2021.795286
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.

    Jasani, Neel / Xu, Xiaonan / Posorske, Benjamin / Kim, Yumi / Vera, Olga / Tsai, Kenneth Y / DeNicola, Gina M / Karreth, Florian A

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Overexpression of PHGDH, the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. ... ...

    Abstract Overexpression of PHGDH, the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. While
    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.11.589139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Squaring the circle: circRNAs in melanoma.

    Mecozzi, Nicol / Vera, Olga / Karreth, Florian A

    Oncogene

    2021  Volume 40, Issue 37, Page(s) 5559–5566

    Abstract: Non-coding RNAs are emerging as critical molecules in the genesis, progression, and therapy resistance of cutaneous melanoma. This includes circular RNAs (circRNAs), a class of non-coding RNAs with distinct characteristics that forms through non- ... ...

    Abstract Non-coding RNAs are emerging as critical molecules in the genesis, progression, and therapy resistance of cutaneous melanoma. This includes circular RNAs (circRNAs), a class of non-coding RNAs with distinct characteristics that forms through non-canonical back-splicing. In this review, we summarize the features and functions of circRNAs and introduce the current knowledge of the roles of circRNAs in melanoma. We also highlight the various mechanisms of action of the well-studied circRNA CDR1as and describe how it acts as a melanoma tumor suppressor. We further discuss the utility of circRNAs as biomarkers, therapeutic targets, and therapeutic agents in melanoma and outline challenges that must be overcome to comprehensively characterize circRNA functions.
    MeSH term(s) Genes, Tumor Suppressor ; Humans ; Melanoma ; RNA Splicing ; RNA, Circular ; Skin Neoplasms ; Melanoma, Cutaneous Malignant
    Chemical Substances RNA, Circular
    Language English
    Publishing date 2021-07-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-021-01977-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Editorial

    Ioannis Grammatikakis / Florian A. Karreth / Amaresh C. Panda

    Frontiers in Molecular Biosciences, Vol

    Structural and Functional Characterization of Circular RNAs

    2021  Volume 8

    Keywords circular RNA ; competing endogenons RNA network ; microRNA ; RNA-bindig proteins ; gene regulaiton ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Pseudogenes as Competitive Endogenous RNAs: Target Prediction and Validation.

    Karreth, Florian A / Ala, Ugo / Provero, Paolo / Pandolfi, Pier Paolo

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2324, Page(s) 115–129

    Abstract: Pseudogenes may regulate expression of their parental genes as well as other protein-coding genes through various mechanisms. One such mechanism is the ability to act as competitive endogenous RNA (ceRNA) and participate in microRNA-mediated cross- ... ...

    Abstract Pseudogenes may regulate expression of their parental genes as well as other protein-coding genes through various mechanisms. One such mechanism is the ability to act as competitive endogenous RNA (ceRNA) and participate in microRNA-mediated cross-regulation. Here, we outline how to predict the targets of pseudogene ceRNAs bioinformatically and how to validate them experimentally.
    MeSH term(s) 3' Untranslated Regions ; Animals ; Cell Line ; Computational Biology/methods ; Gene Silencing ; Genomics/methods ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Pseudogenes/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Small Interfering ; Regulatory Sequences, Ribonucleic Acid/genetics ; Transfection
    Chemical Substances 3' Untranslated Regions ; MicroRNAs ; RNA, Messenger ; RNA, Small Interfering ; Regulatory Sequences, Ribonucleic Acid
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1503-4_8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Genetically engineered mouse models of head and neck cancers.

    Tasoulas, Jason / Srivastava, Sonal / Xu, Xiaonan / Tarasova, Valentina / Maniakas, Anastasios / Karreth, Florian A / Amelio, Antonio L

    Oncogene

    2023  Volume 42, Issue 35, Page(s) 2593–2609

    Abstract: The head and neck region is one of the anatomic sites commonly afflicted by cancer, with ~1.5 million new diagnoses reported worldwide in 2020 alone. Remarkable progress has been made in understanding the underlying disease mechanisms, personalizing care ...

    Abstract The head and neck region is one of the anatomic sites commonly afflicted by cancer, with ~1.5 million new diagnoses reported worldwide in 2020 alone. Remarkable progress has been made in understanding the underlying disease mechanisms, personalizing care based on each tumor's individual molecular characteristics, and even therapeutically exploiting the inherent vulnerabilities of these neoplasms. In this regard, genetically engineered mouse models (GEMMs) have played an instrumental role. While progress in the development of GEMMs has been slower than in other major cancer types, several GEMMs are now available that recapitulate most of the heterogeneous characteristics of head and neck cancers such as the tumor microenvironment. Different approaches have been employed in GEMM development and implementation, though each can generally recapitulate only certain disease aspects. As a result, appropriate model selection is essential for addressing specific research questions. In this review, we present an overview of all currently available head and neck cancer GEMMs, encompassing models for head and neck squamous cell carcinoma, nasopharyngeal carcinoma, and salivary and thyroid gland carcinomas.
    MeSH term(s) Mice ; Animals ; Disease Models, Animal ; Head and Neck Neoplasms/genetics ; Squamous Cell Carcinoma of Head and Neck/genetics ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2023-07-20
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 639046-8
    ISSN 1476-5594 ; 0950-9232
    ISSN (online) 1476-5594
    ISSN 0950-9232
    DOI 10.1038/s41388-023-02783-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis.

    Xu, Xiaonan / Bok, Ilah / Jasani, Neel / Wang, Kaizhen / Chadourne, Manon / Mecozzi, Nicol / Deng, Ou / Welsh, Eric A / Kinose, Fumi / Rix, Uwe / Karreth, Florian A

    Cancer research

    2024  Volume 84, Issue 3, Page(s) 388–404

    Abstract: Inactivating mutations in PTEN are prevalent in melanoma and are thought to support tumor development by hyperactivating the AKT/mTOR pathway. Conversely, activating mutations in AKT are relatively rare in melanoma, and therapies targeting AKT or mTOR ... ...

    Abstract Inactivating mutations in PTEN are prevalent in melanoma and are thought to support tumor development by hyperactivating the AKT/mTOR pathway. Conversely, activating mutations in AKT are relatively rare in melanoma, and therapies targeting AKT or mTOR have shown disappointing outcomes in preclinical models and clinical trials of melanoma. This has led to the speculation that PTEN suppresses melanoma by opposing AKT-independent pathways, potentially through noncanonical functions beyond its lipid phosphatase activity. In this study, we examined the mechanisms of PTEN-mediated suppression of melanoma formation through the restoration of various PTEN functions in PTEN-deficient cells or mouse models. PTEN lipid phosphatase activity predominantly inhibited melanoma cell proliferation, invasion, and tumor growth, with minimal contribution from its protein phosphatase and scaffold functions. A drug screen underscored the exquisite dependence of PTEN-deficient melanoma cells on the AKT/mTOR pathway. Furthermore, activation of AKT alone was sufficient to counteract several aspects of PTEN-mediated melanoma suppression, particularly invasion and the growth of allograft tumors. Phosphoproteomics analysis of the lipid phosphatase activity of PTEN validated its potent inhibition of AKT and many of its known targets, while also identifying the AP-1 transcription factor FRA1 as a downstream effector. The restoration of PTEN dampened FRA1 translation by inhibiting AKT/mTOR signaling, and FRA1 overexpression negated aspects of PTEN-mediated melanoma suppression akin to AKT. This study supports AKT as the key mediator of PTEN inactivation in melanoma and identifies an AKT/mTOR/FRA1 axis as a driver of melanomagenesis.
    Significance: PTEN suppresses melanoma predominantly through its lipid phosphatase function, which when lost, elevates FRA1 levels through AKT/mTOR signaling to promote several aspects of melanomagenesis.
    MeSH term(s) Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism ; Melanoma/genetics ; Melanoma/metabolism ; Signal Transduction/genetics ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Cell Proliferation ; Lipids
    Chemical Substances Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Lipids
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-23-1730
    Database MEDical Literature Analysis and Retrieval System OnLINE

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