Dataset Information

Functional annotation of human long noncoding RNAs via molecular phenotyping.

ABSTRACT: Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.

SUBMITTER: Ramilowski JA

PROVIDER: S-EPMC7397864 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Functional annotation of human long noncoding RNAs via molecular phenotyping.

Ramilowski Jordan A JA Yip Chi Wai CW Agrawal Saumya S Chang Jen-Chien JC Ciani Yari Y Kulakovskiy Ivan V IV Mendez Mickaël M Ooi Jasmine Li Ching JLC Ouyang John F JF Parkinson Nick N Petri Andreas A Roos Leonie L Severin Jessica J Yasuzawa Kayoko K Abugessaisa Imad I Akalin Altuna A Antonov Ivan V IV Arner Erik E Bonetti Alessandro A Bono Hidemasa H Borsari Beatrice B Brombacher Frank F Cameron Christopher JF CJ Cannistraci Carlo Vittorio CV Cardenas Ryan R Cardon Melissa M Chang Howard H Dostie Josée J Ducoli Luca L Favorov Alexander A Fort Alexandre A Garrido Diego D Gil Noa N Gimenez Juliette J Guler Reto R Handoko Lusy L Harshbarger Jayson J Hasegawa Akira A Hasegawa Yuki Y Hashimoto Kosuke K Hayatsu Norihito N Heutink Peter P Hirose Tetsuro T Imada Eddie L EL Itoh Masayoshi M Kaczkowski Bogumil B Kanhere Aditi A Kawabata Emily E Kawaji Hideya H Kawashima Tsugumi T Kelly S Thomas ST Kojima Miki M Kondo Naoto N Koseki Haruhiko H Kouno Tsukasa T Kratz Anton A Kurowska-Stolarska Mariola M Kwon Andrew Tae Jun ATJ Leek Jeffrey J Lennartsson Andreas A Lizio Marina M López-Redondo Fernando F Luginbühl Joachim J Maeda Shiori S Makeev Vsevolod J VJ Marchionni Luigi L Medvedeva Yulia A YA Minoda Aki A Müller Ferenc F Muñoz-Aguirre Manuel M Murata Mitsuyoshi M Nishiyori Hiromi H Nitta Kazuhiro R KR Noguchi Shuhei S Noro Yukihiko Y Nurtdinov Ramil R Okazaki Yasushi Y Orlando Valerio V Paquette Denis D Parr Callum J C CJC Rackham Owen J L OJL Rizzu Patrizia P Sánchez Martinez Diego Fernando DF Sandelin Albin A Sanjana Pillay P Semple Colin A M CAM Shibayama Youtaro Y Sivaraman Divya M DM Suzuki Takahiro T Szumowski Suzannah C SC Tagami Michihira M Taylor Martin S MS Terao Chikashi C Thodberg Malte M Thongjuea Supat S Tripathi Vidisha V Ulitsky Igor I Verardo Roberto R Vorontsov Ilya E IE Yamamoto Chinatsu C Young Robert S RS Baillie J Kenneth JK Forrest Alistair R R ARR Guigó Roderic R Hoffman Michael M MM Hon Chung Chau CC Kasukawa Takeya T Kauppinen Sakari S Kere Juha J Lenhard Boris B Schneider Claudio C Suzuki Harukazu H Yagi Ken K de Hoon Michiel J L MJL Shin Jay W JW Carninci Piero P

Genome research 20200727 7

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular ...[more]

PMID: 32718982

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Project description:Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 downregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells in vitro was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB.

Dataset Information

Functional annotation of human long noncoding RNAs via molecular phenotyping.

Publications

Functional annotation of human long noncoding RNAs via molecular phenotyping.

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