Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA <i>CCAT2</i> induce myeloid malignancies via unique SNP-specific RNA mutations

Shah, Maitri; Ferracin, Manuela; Pileczki, Valentina; Chen, Baoqing; Redis, Roxana S.; Fabris, Linda; Zhang, Xinna; Ivan, Cristina; Shimizu, Masayoshi; Rodríguez-Aguayo, Cristian; Dragomir, Mihnea P.; Roosbroeck, Katrien Van; Almeida, Maria Inês; Ciccone, Maria; Nedelcu, Daniela; Cortez, María Angélica; Manshouri, Taghi; Calin, Steliana; Müftüoğlu, Muharrem; Banerjee, Pinaki P.; Badiwi, Mustafa H.; Parker-Thornburg, Jan; Multani, Asha S.; Welsh, James W.; Estécio, Marcos R.H.; Ling, Hui; Tomuleasa, Ciprian; Dima, Delia; Yang, Hui; Alvarez, Hector A.; You, M. James; Radovich, Milan; Shpall, Elizabeth J.; Fabbri, Muller; Rezvani, Katy; Girnita, Leonard; Berindan‐Neagoe, Ioana; Maitra, Anirban; Verstovšek, Srđan; Fodde, Riccardo; Bueso‐Ramos, Carlos E.; Gagea, Mihai; Manero, Guillermo Garcia

doi:10.1101/gr.225128.117

Cited by 59 publications

(56 citation statements)

References 35 publications

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“…In recent years, lots of important trait-associated variants within lncRNAs have been identified using high-throughput methods such as genome-wide association studies (GWAS) and whole-genome sequencing [56][57][58] . Most of these variants are disease-associated variants in human and model animals such as mouse 59,60 .…”

Section: Discussionmentioning

confidence: 99%

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

Liu

Zhang

et al. 2020

Commun Biol

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Long intergenic non-coding RNAs (lincRNAs) have been proved to be involved in regulating female reproduction. However, to what extent lincRNAs are involved in ovarian functions and fertility is incompletely understood. Here we show that a lincRNA, NORFA is involved in granulosa cell apoptosis, follicular atresia and sow fertility. We found that NORFA was downregulated during follicular atresia, and inhibited granulosa cell apoptosis. NORFA directly interacted with miR-126 and thereby preventing it from binding to TGFBR2 3′-UTR. miR-126 enhanced granulosa cell apoptosis by attenuating NORFA-induced TGF-β signaling pathway. Importantly, a breed-specific 19-bp duplication was detected in NORFA promoter, which proved association with sow fertility through enhancing transcription activity of NORFA by recruiting transcription factor NFIX. In summary, our findings identified a candidate lincRNA for sow prolificacy, and provided insights into the mechanism of follicular atresia and female fertility.

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Section: Discussionmentioning

confidence: 99%

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

Liu

Zhang

et al. 2020

Commun Biol

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“…Although the pyknons are located in about 225,000 places within the human genome, other more abundant genetic elements influence the structure of ncRNAs, and these are the SNPs. The examples of SNPs influencing the function of ncRNAs through the structural changes in ncRNAs are increasing at a rapid pace (Castellanos-Rubio et al 2016; Redis et al 2016;Bal et al 2017;Shah et al 2018).…”

Section: Box 2 Inter-and Intra-genomic Conservation Of Ies and Sesmentioning

confidence: 99%

Decrypting noncoding RNA interactions, structures, and functional networks

et al. 2019

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The world of noncoding RNAs (ncRNAs) is composed of an enormous and growing number of transcripts, ranging in length from tens of bases to tens of kilobases, involved in all biological processes and altered in expression and/or function in many types of human disorders. The premise of this review is the concept that ncRNAs, like many large proteins, have a multidomain architecture that organizes them spatially and functionally. As ncRNAs are beginning to be imprecisely classified into functional families, we review here how their structural properties might inform their functions with focus on structural architecture-function relationships. We will describe the properties of "interactor elements" (IEs) involved in direct physical interaction with nucleic acids, proteins, or lipids and of "structural elements" (SEs) directing their wiring within the "ncRNA interactor networks" through the emergence of secondary and/or tertiary structures. We suggest that spectrums of "letters" (ncRNA elements) are assembled into "words" (ncRNA domains) that are further organized into "phrases" (complete ncRNA structures) with functional meaning (signaling output) through complex "sentences" (the ncRNA interactor networks). This semiotic analogy can guide the exploitation of ncRNAs as new therapeutic targets through the development of IE-blockers and/or SE-lockers that will change the interactor partners' spectrum of proteins, RNAs, DNAs, or lipids and consequently influence disease phenotypes.

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“…In contrast to mRNAs, lncRNAs, have little or no translation potential [66] . LncRNAs can execute several functions working as scaffolds, guidance molecules, signaling pathways, and be decoys for other molecules [67][68][69] . Additionally, these long RNA molecules regulate gene expression by recruiting, to a specific DNA region, epigenetics modifiers or chromatin-remodelling complexes [66] .…”

Section: Roles Of Exosomal Lncrnasmentioning

confidence: 99%

The role of exosomal long non-coding RNAs in cancer drug resistance

Santos

Dragomir

2019

CDR

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One of the major challenges in oncology is drug resistance, which triggers relapse and shortens patients' survival. In order to promote drug desensitization, cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific conditions. To achieve this objective, cellular communication is a key factor. Classically, cells were believed to restrictively communicate by ligand-receptor binding, physical cell-to-cell interactions and synapses. Nevertheless, the crosstalk between tumor cells and stroma cells has also been recently reported to be mediated through exosomes, the smallest extracellular vesicles, which transport a plethora of functionally active molecules, such as: proteins, lipids, messenger RNA, DNA, microRNA or long non-coding RNA (lncRNAs). LncRNAs are RNA molecules greater than 200 base pairs that are deregulated in cancer and other diseases. Exosomal lncRNAs are highly stable and can be found in several body fluids, being considered potential biomarkers for tumor liquid biopsy. Exosomal lncRNAs promote angiogenesis, cell proliferation and drug resistance. The role of exosomal lncRNAs in drug resistance affects the main treatment strategies in oncology: chemotherapy, targeted therapy, hormone therapy and immunotherapy. Overall, knowing the molecular mechanisms by which exosomal lncRNA induce pharmacologic resistance could improve further drug development and identify drug resistance biomarkers.

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Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations

Cited by 59 publications

References 35 publications

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

NORFA, long intergenic noncoding RNA, maintains sow fertility by inhibiting granulosa cell death

Decrypting noncoding RNA interactions, structures, and functional networks

The role of exosomal long non-coding RNAs in cancer drug resistance

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