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  1. Article ; Online: Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens

    Inês A. M. Barbosa / Rajaraman Gopalakrishnan / Samuele Mercan / Thanos P. Mourikis / Typhaine Martin / Simon Wengert / Caibin Sheng / Fei Ji / Rui Lopes / Judith Knehr / Marc Altorfer / Alicia Lindeman / Carsten Russ / Ulrike Naumann / Javad Golji / Kathleen Sprouffske / Louise Barys / Luca Tordella / Dirk Schübeler /
    Tobias Schmelzle / Giorgio G. Galli

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 15

    Abstract: Abstract YAP is a key transcriptional co-activator of TEADs, it regulates cell growth and is frequently activated in cancer. In Malignant Pleural Mesothelioma (MPM), YAP is activated by loss-of-function mutations in upstream components of the Hippo ... ...

    Abstract Abstract YAP is a key transcriptional co-activator of TEADs, it regulates cell growth and is frequently activated in cancer. In Malignant Pleural Mesothelioma (MPM), YAP is activated by loss-of-function mutations in upstream components of the Hippo pathway, while, in Uveal Melanoma (UM), YAP is activated in a Hippo-independent manner. To date, it is unclear if and how the different oncogenic lesions activating YAP impact its oncogenic program, which is particularly relevant for designing selective anti-cancer therapies. Here we show that, despite YAP being essential in both MPM and UM, its interaction with TEAD is unexpectedly dispensable in UM, limiting the applicability of TEAD inhibitors in this cancer type. Systematic functional interrogation of YAP regulatory elements in both cancer types reveals convergent regulation of broad oncogenic drivers in both MPM and UM, but also strikingly selective programs. Our work reveals unanticipated lineage-specific features of the YAP regulatory network that provide important insights to guide the design of tailored therapeutic strategies to inhibit YAP signaling across different cancer types.
    Keywords Science ; Q
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: An Optimized microRNA Backbone for Effective Single-Copy RNAi

    Christof Fellmann / Thomas Hoffmann / Vaishali Sridhar / Barbara Hopfgartner / Matthias Muhar / Mareike Roth / Dan Yu Lai / Inês A.M. Barbosa / Jung Shick Kwon / Yuanzhe Guan / Nishi Sinha / Johannes Zuber

    Cell Reports, Vol 5, Iss 6, Pp 1704-

    2013  Volume 1713

    Abstract: Short hairpin RNA (shRNA) technology enables stable and regulated gene repression. For establishing experimentally versatile RNAi tools and minimizing toxicities, synthetic shRNAs can be embedded into endogenous microRNA contexts. However, due to our ... ...

    Abstract Short hairpin RNA (shRNA) technology enables stable and regulated gene repression. For establishing experimentally versatile RNAi tools and minimizing toxicities, synthetic shRNAs can be embedded into endogenous microRNA contexts. However, due to our incomplete understanding of microRNA biogenesis, such “shRNAmirs” often fail to trigger potent knockdown, especially when expressed from a single genomic copy. Following recent advances in design of synthetic shRNAmir stems, here we take a systematic approach to optimize the experimental miR-30 backbone. Among several favorable features, we identify a conserved element 3′ of the basal stem as critically required for optimal shRNAmir processing and implement it in an optimized backbone termed “miR-E”, which strongly increases mature shRNA levels and knockdown efficacy. Existing miR-30 reagents can be easily converted to miR-E, and its combination with up-to-date design rules establishes a validated and accessible platform for generating effective single-copy shRNA libraries that will facilitate the functional annotation of the genome.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2013-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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