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2017 ; 8
(46
): 80223-80234
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Long non-coding RNA profile in mantle cell lymphoma identifies a functional
lncRNA ROR1-AS1 associated with EZH2/PRC2 complex
#MMPMID29113297
Hu G
; Gupta SK
; Troska TP
; Nair A
; Gupta M
Oncotarget
2017[Oct]; 8
(46
): 80223-80234
PMID29113297
show ga
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by
rapid disease progression. The needs for new therapeutic strategies for MCL
patients call for further understanding on the molecular mechanisms of
pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized
as key regulators of gene expression and disease development, however, the role
of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next
generation RNA-sequencing was carried out on MCL patient samples along with
normal controls and data was analyzed. As a result, several novel lncRNAs were
found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the
most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and
ectopically transfected in MCL cell lines. Results showed that overexpression of
ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the
treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also
decreased the mRNA expression of P16 (P = 0.21), and SOX11 (p = 0.017), without
much effect on P53, ATM and P14 mRNA. RNA-immunoprecipitation assays demonstrated
high affinity binding of lncRNA ROR1-AS1 with EZH2 and SUZ12 proteins of the
polycomb repressive complex-2 (PRC2). Suppressing EZH2 activity with
pharmacological inhibitor GSK343 abolished binding of ROR1-AS1 with EZH2. Taken
together, this study identified a functional lncRNA ROR-AS1 involved with
regulation of gene transcription via associating with PRC2 complex, and may serve
as a novel biomarker in MCL patients.