LncRNAs downregulated in childhood acute lymphoblastic leukemia modulate
apoptosis, cell migration, and DNA damage response
#MMPMID29113332
Gioia R
; Drouin S
; Ouimet M
; Caron M
; St-Onge P
; Richer C
; Sinnett D
Oncotarget
2017[Oct]; 8
(46
): 80645-80650
PMID29113332
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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 ?-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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