{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:30:14Z","timestamp":1794047414477,"version":"4.8.0"},"reference-count":27,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"1","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Long non-coding RNA NEAT1 is the core structural component of the nuclear paraspeckle (PS) organelles and it has been found to be deregulated in multiple myeloma (MM) patients. Experimental evidence indicated that NEAT1 silencing negatively impacts proliferation and viability of MM cells, both in vitro and in vivo, suggesting a role in DNA damage repair (DDR). In order to elucidate the biological and molecular relevance of NEAT1 upregulation in MM disease we exploited the CRISPR\/Cas9 synergistic activation mediator genome editing system to engineer the AMO-1 MM cell line and generate two clones that para-physiologically transactivate NEAT1 at different levels. NEAT1 overexpression is associated with oncogenic and prosurvival advantages in MM cells exposed to nutrient starvation or a hypoxic microenvironment, which are stressful conditions often associated with more aggressive disease phases. Furthermore, we highlighted the NEAT1 involvement in virtually all DDR processes through, at least, two different mechanisms. On one side NEAT1 positively regulates the posttranslational stabilization of essential PS proteins, which are involved in almost all DDR systems, thus increasing their availability within cells. On the other hand, NEAT1 plays a crucial role as a major regulator of a molecular axis that includes ATM and the catalytic subunit of DNA-PK kinase proteins, and their direct targets pRPA32 and pCHK2. Overall, we provided novel important insightsthe role of NEAT1 in supporting MM cells adaptation to stressful conditions by improving the maintenance of DNA integrity. Taken together, our results suggest that NEAT1, and probably PS organelles, could represent a potential therapeutic target for MM treatment.<\/jats:p>","DOI":"10.3324\/haematol.2022.281167","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T03:37:45Z","timestamp":1662608265000},"page":"219-233","source":"Crossref","is-referenced-by-count":24,"title":["Activation of long non-coding RNA NEAT1 leads to survival advantage of multiple myeloma cells by supporting a positive regulatory loop with DNA repair proteins"],"prefix":"10.3324","volume":"108","author":[{"given":"Elisa","family":"Taiana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bandini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Katia","family":"Favasuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Ronchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Silvestris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Puccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Todoerti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Erratico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Giannandrea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Bolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Amodio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Ciarrocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Chiaramonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Torrente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Piva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2022,9,8]]},"reference":[{"key":"43319","doi-asserted-by":"crossref","unstructured":"Bolli N, Biancon G, Moarii M. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia. 2018; 32(12):2604-2616.","DOI":"10.1038\/s41375-018-0037-9"},{"key":"43320","doi-asserted-by":"crossref","unstructured":"Munshi NC, Anderson KC. New strategies in the treatment of multiple myeloma. Clin Cancer Res. 2013; 19(13):3337-3344.","DOI":"10.1158\/1078-0432.CCR-12-1881"},{"key":"43321","doi-asserted-by":"crossref","unstructured":"Amodio N, Stamato MA, Juli G. Drugging the lncRNA MALAT1 via LNA gapmeR ASO inhibits gene expression of proteasome subunits and triggers anti-multiple myeloma activity. Leukemia. 2018; 32(9):1948-1957.","DOI":"10.1038\/s41375-018-0067-3"},{"key":"43322","doi-asserted-by":"crossref","unstructured":"Huarte M. The emerging role of lncRNAs in cancer. Nature Med. 2015; 21(11):1253-1261.","DOI":"10.1038\/nm.3981"},{"key":"43323","doi-asserted-by":"crossref","unstructured":"Morelli E, Gulla A, Rocca R. The non-coding RNA landscape of plasma cell dyscrasias. Cancers. 2020; 12(2):320.","DOI":"10.3390\/cancers12020320"},{"key":"43324","doi-asserted-by":"crossref","unstructured":"Taiana E, Favasuli V, Ronchetti D. Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma. Leukemia. 2020; 34(1):234-244.","DOI":"10.1038\/s41375-019-0542-5"},{"key":"43325","doi-asserted-by":"crossref","unstructured":"Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-914.","DOI":"10.1016\/j.molcel.2011.08.018"},{"key":"43326","doi-asserted-by":"crossref","unstructured":"Taiana E, Ronchetti D, Favasuli V. Long non-coding RNA NEAT1 shows high expression unrelated to molecular features and clinical outcome in multiple myeloma. Haematologica. 2019; 104(2):e72-e76.","DOI":"10.3324\/haematol.2018.201301"},{"key":"43327","doi-asserted-by":"crossref","unstructured":"Taiana E, Ronchetti D, Todoerti K. LncRNA NEAT1 in paraspeckles: a structural scaffold for cellular DNA damage response systems?. Noncoding RNA. 2020; 6(3):26.","DOI":"10.3390\/ncrna6030026"},{"key":"43328","doi-asserted-by":"crossref","unstructured":"Yu X, Li Z, Zheng H, Chan MT, Wu WK. NEAT1: a novel cancer-related long non-coding RNA. Cell Prolif. 2017; 50(2):e12329.","DOI":"10.1111\/cpr.12329"},{"key":"43329","doi-asserted-by":"crossref","unstructured":"Guru SC, Agarwal SK, Manickam P. A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus. Genome Res. 1997; 7(7):725-735.","DOI":"10.1101\/gr.7.7.725"},{"key":"43330","doi-asserted-by":"crossref","unstructured":"Naganuma T, Nakagawa S, Tanigawa A. Alternative 3'-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J. 2012; 31(20):4020-4034.","DOI":"10.1038\/emboj.2012.251"},{"key":"43331","doi-asserted-by":"crossref","unstructured":"Li K, Yao T, Zhang Y, Li W, Wang Z. NEAT1 as a competing endogenous RNA in tumorigenesis of various cancers: role, mechanism and therapeutic potential. Int J Biol Sci. 2021; 17(13):3428-3440.","DOI":"10.7150\/ijbs.62728"},{"key":"43332","doi-asserted-by":"crossref","unstructured":"Adriaens C, Marine JC. NEAT1-containing paraspeckles: central hubs in stress response and tumor formation. Cell Cycle. 2017; 16(2):137-138.","DOI":"10.1080\/15384101.2016.1235847"},{"key":"43333","doi-asserted-by":"crossref","unstructured":"Adriaens C, Standaert L, Barra J. p53 induces formation of NEAT1 lncRNA-containing paraspeckles that modulate replication stress response and chemosensitivity. Nat Med. 2016; 22(8):861-868.","DOI":"10.1038\/nm.4135"},{"key":"43334","doi-asserted-by":"crossref","unstructured":"Blume CJ, Hotz-Wagenblatt A, Hullein J. p53-dependent non-coding RNA networks in chronic lymphocytic leukemia. 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