An unbiased lncRNAs dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a potential therapeutic target for Multiple Myeloma
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PROVIDER: PRJNA1143216 | ENA |
REPOSITORIES: ENA
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Project description:Multiple Myeloma (MM) is an incurable malignancy characterised by alterations of coding and non-coding genes that promote tumour growth and drug resistance. Despite the crucial role of long non-coding-RNAs (lncRNAs) in myeloma genesis is established, the functional role of the non-coding RNAome in MM remains largely unknown. We performed an unbiased CRISPR-Cas9 recessive screen targeting 671 lncRNAs in MM cell lines unvealing and prioritising a list of novel onco-lncRNAs essential for MM cell fitness and associated with high expression and poor prognosis in MM patients. Among them, RP11-350G8.5 emerged as the most promising vulnerability for MM cells, irrespective of their resistance to the standard-of-care bortezomib. We i) validated the oncogenic role of RP11-350G8.5 in vitro and in vivo; ii) characterised its function in relation to the unfolded protein stress response and induction of immunogenic cell death, and iii) shed light on its sub-cellular localisation, structural and chemical predictions of RNA-G-quadruplex-forming regions to pave the way to the development of novel therapeutics.
2024-08-20 | GSE273796 | GEO
Project description:Downregulations of TCAM1P-004 and RP11-598D14.1 were frequently observed in HCC tumors as compared to adjacent non-tumor tissues. To further study the molecular functions of TCAM1P-004 and RP11-598D14.1, we attempted to identify the gene targets regulated by either lncRNAs. Knockdown of TCAM1P-004 or RP11-598D14.1 were achieved by transduction of lentivirus carrying respective shRNAs in non-tumor hepatocyte MIHA cells. Diffferentially expressed genes after knockdown of the lncRNAs were compared to cells tranduced with lentivirus carrying scramble shRNAs.
2018-10-24 | E-MTAB-7280 | biostudies-arrayexpress
Project description:To further explore t of the role lncRNAs in glaucoma patients, we have employed lncRNAs microarray expression profiling as a discovery platform to identify abnormal genes under oxidative stress in HTMCs. Our results revealed that lncRNA-RP11 was significantly up-regulated under oxidative stress in HTMCs. Further studies found that lncRNA-RP11-820 directly binds miR-3178, through which regulates the expression of MYOD1. Importantly, MYOD1 can transcriptionally activate ECM genes. Furthermore, MYOD1 binds STAT3 to form a transcription complex, and transcriptionally activates ECM genes expression in HTMCs. Taken together, our data established taht oxidative stress induced lncRNA-RP11-820 plays a key role in regulating miR-3178/MYOD1/ECM axis in HTMCs.
2019-02-07 | GSE126170 | GEO
Project description:Methods and Materials The high throughput RNA sequencing (RNA-seq) data from kidney biopsies of LN patients and controls was applied studied to screen for candidate lncRNAs. Quantitative real-time polymerase chain reaction(RT-qPCR) was used to detect the expression of lncRNAs and individual IFN-stimulated genes (ISGs). Western blotting and dual-luciferace luciferase reporter assay was adopted to explore the specific function of the candidate lncRNA. Results The expression of lncRNA RP11-2B6.2 was significantly increased in the kidney tissues from LN patients compared with those from healthy controls, and positive correlated with the degree of disease activity and renal injuryinjuries. Additionally, expression of LncRNA RP11-2B6.2 could be stimulated by type I IFN. Silencing it RP11-2B6.2 significantly reduced the expression of a group of interferon-stimulating genes(ISGs) including IFIT1, OAS1, etc., Furthermore, it lncRNA RP11-2B6.2 affected the expression of IFN alpha and beta receptor subunit 1 (IFNAR1), phosphorylation of Jak1 and Stat1, and the luciferase activity induced by interferon stimulated response element(ISRE). Conclusion Long noncoding RNA RP11-2B6.2 is a positive regulator of the type I IFN signaling pathway in LN. It LncRNA RP11-2B6.2 may contribute to the pathogenesis of LN and provide served as a potentially therapeutic target.
2019-05-01 | GSE98422 | GEO
Project description:Transfection experiments aimed at understanding the impact of upregulation a lncRNA (RP11-326A19.4) on genome-wide transcription
2019-06-11 | GSE132451 | GEO
Project description:Through deep RNA-seq of human monocyte-derived macrophages, we identified RP11-184M15.1, a human macrophage-specific lincRNA, to be highly induced in the cytoplasm of IL-4-stimulated macrophage. Preliminary data showed that treatment of IL-4-stimulated THP1 human macrophages with RP11-184M15.1 small interfering RNA (siRNA) repressed apoptosis of resolving macrophages, as shown by decreased Annexin V+ macrophages, and reduced protein expression of cleaved PARP. Biotinylated RP11-184M15.1 pulldown coupled with mass spectrometry indicated an interaction between RP11-184M15.1 and zinc finger RNA-binding protein (ZFR). RIP corroborated the proposed interaction between RP11-184M15.1 and ZFR. RNAInter revealed mRNAs predicted to interact with ZFR, and some of those genes (e.g., ALYREF, CCNYL1) were also differentially expressed in RNA-seq data of control versus RP11-184M15.1 knockdown in IL-4-stimulated THP1 macrophages. qPCR validated that ALYREF and CCNYL1 expression are reduced with RP11-184M15.1 knockdown. In contrast, with ZFR siRNA, ALYREF and CCNYL1 mRNA expressions were elevated. Thus, a hypothesis to be further tested is that RP11-184M15.1 interacts with ZFR to regulate mRNA stability in IL-4-stimulated macrophages. Nuclear RNA export factor 1 (NXF1) was also validated by RIP to interact with RP11-184M15.1. NXF1 is a known interacting partner of ALYREF in the transcription-export (TREX) complex. With RP11-184M15.1 knockdown, the protein level of ALYREF decreased, and Ingenuity Pathway Analysis (IPA) of RNA-seq data of control versus RP11-184M15.1 knockdown revealed that THO complex subunit 5 homolog (THOC5), another component of the TREX complex, may be an upstream regulator. In addition, past studies have revealed that ALYREF and NXF1 are involved in nuclear export of inflammatory mRNAs and proinflammatory macrophage phenotype, respectively. With RP11-184M15.1 knockdown, there was decreased expression of inflammatory macrophage-associated genes. It may be possible that RP11-184M15.1 functions in mRNA export, along with NXF1 and ALYREF.
2022-11-23 | GSE218308 | GEO
Project description:dCas9 activation of RP11-326A19.4
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Project description:Transfection experiments aimed at understanding the impact of upregulating lncRNA RP11-326A19.4 on the transcriptome; follow-up of GSE132451
2019-12-17 | GSE142097 | GEO
Project description:Deletion experiment aimed at understanding the role of lncRNA RP11-326A19.4 /CARMAL via its deletion. The impact on of the deletion on the transcriptome was assessed by array analysis.
2019-12-17 | GSE142098 | GEO
Project description:Paraburkholderia madseniana strain:RP11 Genome sequencing and assembly
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