Nature communications, 2021-04, Vol.12 (1), p.2038-2038, Article 2038
2021
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- Autor(en) / Beteiligte
- Titel
- A KRAS-responsive long non-coding RNA controls microRNA processing
- Ist Teil von
- Nature communications, 2021-04, Vol.12 (1), p.2038-2038, Article 2038
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- Wild-type KRAS ( KRAS WT ) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRAS WT overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically, KIMAT1 is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex. KIMAT1 knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for KIMAT1 in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with KIMAT1 could be a strategy to hamper KRAS-induced tumorigenesis. Wild-type KRAS amplification is known to induce KRAS activation in cancer leading to poor prognostic outcomes. Here the authors identify a KRAS-responsive lncRNA, KIMAT1 that maintains KRAS signalling in lung cancer, suggesting that its targeting may prevent KRAS-driven tumourigenesis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-22337-3Titel-ID: cdi_doaj_primary_oai_doaj_org_article_befd75df391041c7bcbc529acaf3af0c
- Format
- –
- Schlagworte
- 13, 13/105, 13/106, 13/109, 13/2, 13/31, 13/44, 13/89, 13/95, 14, 45, 45/15, 45/61, 45/71, 631/337/384/2568, 692/4028/67/1612/1350, A549 Cells, Amplification, Animals, Carcinoma, Non-Small-Cell Lung - genetics, Carcinoma, Non-Small-Cell Lung - metabolism, Carcinoma, Non-Small-Cell Lung - therapy, Cell Line, Tumor, Control theory, Feedback loops, Female, Gene Expression Profiling - methods, Gene Expression Regulation, Neoplastic, Gene Ontology, Humanities and Social Sciences, Humans, In vivo methods and tests, K-Ras protein, Kaplan-Meier Estimate, Lung cancer, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - therapy, Mice, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, MicroRNAs, MicroRNAs - genetics, miRNA, multidisciplinary, Myc protein, Non-coding RNA, Nucleophosmin, Positive feedback, Proto-Oncogene Proteins p21(ras) - genetics, Proto-Oncogene Proteins p21(ras) - metabolism, Ribonucleic acid, RNA, RNA processing, RNA, Long Noncoding - genetics, Science, Science (multidisciplinary), Signaling, Tumor cell lines, Tumor suppressor genes, Tumorigenesis, Xenograft Model Antitumor Assays - methods