biostudies-literatureUnknown144(16)Grillone K<h4>Abstract</h4>Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)-resistant derivative. To rank functionally and clinically relevant candidates, we designed and used a bioinformatic prioritization pipeline combining functional data from cellular screens with prognostic and transcriptional data from patients with MM. With this approach, we unveiled and prioritized 8 onco-lncBlood1705-1721https://www.ebi.ac.uk/biostudies/studies/S-EPMC11522894biostudies-literatureAn unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma.PMC11522894Riillo CCroci OBrancaccio DPagano BCremaschi PTassone PConforti FAscrizzi SRandazzo AAlcaro SIorio FTagliaferri PPolera NGraziano RAmato JCaracciolo DGrillone KRocca RfalseAn unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma.<h4>Abstract</h4>Multiple myeloma (MM) is an incurable malignancy characterized by altered expression of coding and noncoding genes promoting tumor growth and drug resistance. Although the crucial role of long noncoding RNAs (lncRNAs) in MM is clearly established, the function of the noncoding RNAome, which might allow the design of novel therapeutics, is largely unknown. We performed an unbiased CRISPR-Cas9 loss-of-function screen of 671 lncRNAs in MM cells and their bortezomib (BZB)-resistant derivative. To rank functionally and clinically relevant candidates, we designed and used a bioinformatic prioritization pipeline combining functional data from cellular screens with prognostic and transcriptional data from patients with MM. With this approach, we unveiled and prioritized 8 onco-lnc2024-01-01T00:00:00Z2024 Oct2026-04-29T23:57:53.194Z2025-04-04T22:47:37.737ZS-EPMC115228943915806610.1182/blood.2023021991