Identification of long non‐coding RNA MVIH as a prognostic marker and therapeutic target in acute myeloid leukemia

Azken urteetan gertatu den genomen ikerketarako teknologien garapen ikaragarriak zientzialariek genoma, transkriptoma eta proteomaren inguruan zuten ikuspegia errotik aldatzea eragin du. DNAren eta RNAren sekuentziazio masiboei esker, ordura arte “DNA zabor” bezala ezagututako guneetatik transkribatutako proteinarik kodetzen ez duten milaka RNA ez-kodetzaile (ncRNA) detektatu dira, genomen inguruko ikuspegi proteozentrikoa alboratuz eta RNA ez-kodetzaileak, bereziki luzeak (long non-coding RNA, lncRNA), ikertzaileen fokuan jarriz. Era berean, azken ikerketek geneen adierazpenerako ezinbestekoak diren transkripzio- eta itzulpen-prozesuen erregulazioak duen garrantzia ere agerian jarri dute. Erregulazio-mekanismo nagusietako bat DNAn, RNAn eta proteinetan aurkitu diren marka biokimiko itzulgarriek osatzen dute; eta horien ikerketak epigenomika, epitranskriptomika eta epiproteomika izeneko biologiaren atal berrien sorrera ekarri du. Hala ere, ikerketa gehienak epigenoma eta epiproteomaren inguruan egin direnez, marka horien ezarpenak RNAn duen eraginak ezezaguna izaten jarraitzen du. Emaitza hauek tarteko, zalantzarik gabe RNAren biologiaren esparruan galdera asko dago oraindik erantzuteko. Hori dela-eta, berrikuspen honetan aipatutako RNAren biologiaren bi esparru berrietan fokuratu gara, horien inguruan ezaguna dena jasoz eta giza gaixotasunekin, zehazki leuzemia mieloide akutuarekin (Acute myeloid leukemia-AML), duten harremana laburbilduz. Oraindik alor ezezagunak izanik, ikertzaileek tamaina eta konplexutasun handiko erronka dute aurrean RNAren biologiaren mundu ilun hau argitu ahal izateko eta emaitza hauek arlo klinikora bideratzeko.

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Prognostic Significance of Long Non Coding RNA ANRIL and SNHG14 in Acute Myeloid Leukemia

Asian Pacific Journal of Cancer Prevention ◽

10.31557/apjcp.2021.22.12.3763 ◽

2021 ◽

Vol 22 (12) ◽

pp. 3763-3771

Author(s):

Marwa Gamaleldin ◽

Omar Ghallab ◽

Reham Abo Elwafa

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Significance ◽

Non Coding Rna ◽

Long Non Coding Rna ◽

Acute Myeloid

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The retinoic acid receptor co-factor NRIP1 is uniquely upregulated and represents a therapeutic target in acute myeloid leukemia with chromosome 3q rearrangements

Haematologica ◽

10.3324/haematol.2021.276048 ◽

2021 ◽

Author(s):

Sarah Grasedieck ◽

Ariene Cabantog ◽

Liam MacPhee ◽

Junbum Im ◽

Christoph Ruess ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Therapeutic Target ◽

Myeloid Leukemia ◽

Integration Site ◽

Retinoic Acid Receptor ◽

Aberrant Expression ◽

Interacting Protein ◽

Disease Subtype ◽

Non Coding Rna ◽

Acute Myeloid

Aberrant expression of Ecotropic Viral Integration Site 1 (EVI1) is a hallmark of acute myeloid leukemia (AML) with inv(3) or t(3;3), which is a disease subtype with especially poor outcome. In studying transcriptomes from AML patients with chromosome 3q rearrangements, we identified a significant upregulation of the Nuclear Receptor Interacting Protein 1 (NRIP1) as well as its adjacent non-coding RNA LOC101927745. Utilizing transcriptomic and epigenomic data from over 900 primary patient samples as well as genetic and transcriptional engineering approaches, we have identified several mechanisms that can lead to upregulation of NRIP1 in AML. We hypothesize that the LOC101927745 transcription start site harbors a context-dependent enhancer that is bound by EVI1, causing upregulation of NRIP1 in AML with chr3 abnormalities. Furthermore, we show that NRIP1 knockdown negatively affects the proliferation and survival of 3q-rearranged AML cells and increases their sensitivity towards ATRA, suggesting that NRIP1 is relevant for the pathogenesis of inv(3)/t(3;3) AML and could serve as a novel therapeutic target in myeloid malignancies with 3q abnormalities.

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