2026-05-22T08:52:25Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/230882024-11-29T08:24:05Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16968
Repisalud
author
Unfried, Juan P
author
Marín-Baquero, Mikel
author
Rivera-Calzada, Ángel
author
Razquin, Nerea
author
Martín-Cuevas, Eva M
author
de Bragança, Sara
author
Aicart-Ramos, Clara
author
McCoy, Christopher
author
Prats-Mari, Laura
author
Arribas-Bosacoma, Raquel
author
Lee, Linda
author
Caruso, Stefano
author
Zucman-Rossi, Jessica
author
Sangro, Bruno
author
Williams, Gareth
author
Moreno-Herrero, Fernando
author
Llorca Blanco, Oscar Antonio
author
Lees-Miller, Susan P
author
Fortes, Puri
author
Llorca, Oscar
author
Unfried, Juan P.
author
Martín-Cuevas, Eva M.
author
Lees-Miller, Susan P
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Economía y Competitividad (España)
funder
Ligue Nationale Contre le Cancer (Francia)
funder
Canada Foundation for Innovation
funder
Asociación Española Contra el Cáncer
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
United States Department of Health and Human Services
funder
Natural Sciences and Engineering Research Council of Canada (NSERC)
2024-09-16T08:16:58Z
2024-09-16T08:16:58Z
2021-10-01
Cancer Res . 2021 ;81(19):4910-4925.
10.1158/0008-5472.CAN-21-0463
1538-7445
0008-5472
Cancer research
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488005/pdf/nihms-1730416.pdf
34321241
https://hdl.handle.net/20.500.12105/23088
Long noncoding RNAs (lncRNA) are emerging as key players in cancer as parts of poorly understood molecular mechanisms. Here, we investigated lncRNAs that play a role in hepatocellular carcinoma (HCC) and identified NIHCOLE, a novel lncRNA induced in HCC with oncogenic potential and a role in the ligation efficiency of DNA double-stranded breaks (DSB). NIHCOLE expression was associated with poor prognosis and survival of HCC patients. Depletion of NIHCOLE from HCC cells led to impaired proliferation and increased apoptosis. NIHCOLE deficiency led to accumulation of DNA damage due to a specific decrease in the activity of the nonhomologous end-joining (NHEJ) pathway of DSB repair. DNA damage induction in NIHCOLE-depleted cells further decreased HCC cell growth. NIHCOLE was associated with DSB markers and recruited several molecules of the Ku70/Ku80 heterodimer. Further, NIHCOLE putative structural domains supported stable multimeric complexes formed by several NHEJ factors including Ku70/80, APLF, XRCC4, and DNA ligase IV. NHEJ reconstitution assays showed that NIHCOLE promoted the ligation efficiency of blunt-ended DSBs. Collectively, these data show that NIHCOLE serves as a scaffold and facilitator of NHEJ machinery and confers an advantage to HCC cells, which could be exploited as a targetable vulnerability. SIGNIFICANCE: This study characterizes the role of lncRNA NIHCOLE in DNA repair and cellular fitness in HCC, thus implicating it as a therapeutic target.See related commentary by Barcena-Varela and Lujambio, p. 4899.
eng
Long Noncoding RNA NIHCOLE Promotes Ligation Efficiency of DNA Double-Strand Breaks in Hepatocellular Carcinoma.
research article