LncRNAs downregulated in childhood acute lymphoblastic leukemia modulate apoptosis, cell migration, and DNA damage response
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Romain Gioia1, Simon Drouin1, Manon Ouimet1, Maxime Caron1, Pascal St-Onge1, Chantal Richer1 and Daniel Sinnett1,2
1Division of Hematology-Oncology, Research Center, Sainte-Justine University Health Center, Montreal, QC, Canada
2Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC, Canada
Daniel Sinnett, email: firstname.lastname@example.org
Keywords: long non-coding RNA, acute lymphoblastic leukemia, DNA damage response, treatment resistance, apoptosis
Received: February 24, 2017 Accepted: August 19, 2017 Published: September 11, 2017
Childhood acute lymphoblastic leukemia (cALL) accounts for 25% of pediatric cancers and is one of the leading causes of disease-related death in children. Although long non-coding RNAs (lncRNAs) have been implicated in cALL etiology, progression, and treatment response, little is known about their exact functional role. We had previously sequenced the whole transcriptome of 56 cALL patients and identified lncRNA transcripts specifically silenced in tumoral cells. Here we investigated the impact of restoring the expression of three of these (RP11-624C23.1, RP11-203E8, and RP11-446E9) in leukemic cell lines had dramatic impact on cancer hallmark cellular phenotypes such as apoptosis, cell proliferation and migration, and DNA damage response. Interestingly, both RP11-624C23.1 and RP11-203E8 had very similar impacts on DNA damage response, specifically displaying lower γ-H2A.X and higher apoptosis levels than control cells in response to genotoxic stress. These results indicate that silencing RP11-624C23.1 or RP11-203E8 could provide a selective advantage to leukemic cells by increasing resistance to genotoxic stress, possibly by modulating the DDR pathway. Since genotoxic agents are fundamental parts of antineoplastic treatment, further investigation of the mechanisms these lncRNAs impact would provide novel and interesting avenues for overcoming treatment resistance.
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