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2017 ; 8
(48
): 84153-84167
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Long non-coding RNA SNHG15 inhibits P15 and KLF2 expression to promote pancreatic
cancer proliferation through EZH2-mediated H3K27me3
#MMPMID29137412
Ma Z
; Huang H
; Wang J
; Zhou Y
; Pu F
; Zhao Q
; Peng P
; Hui B
; Ji H
; Wang K
Oncotarget
2017[Oct]; 8
(48
): 84153-84167
PMID29137412
show ga
Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple
cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to
be up-regulated in gastric cancer and hepatocellular carcinoma, exerting
oncogenic effects. Nevertheless, the biological function and regulatory mechanism
of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported
that SNHG15 expression was also upregulated in PC tissues, and its overexpression
was remarkably associated with tumor size, tumor node metastasis (TNM) stage and
lymph node metastasis in patients with PC. SNHG15 knockdown inhibited
proliferative capacities and suppressed apoptotic rate of PC cells in vitro, and
impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP)
assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like
factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and
chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was
capable of binding to promoter regions of P15 and KLF2 to induce histone H3
lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated
that SNHG15 oncogenic function partially involved P15 and KLF2 repression.
Consistently, an inverse correlation between the expression of SNHG15 and traget
genes were found in PC tissues. Our results reported that SNHG15 could act as an
oncogene in PC, revealing its potential value as a biomarker for early detection
and individualized therapy.