Xue Wang;Wen Sun;Weifeng Shen;Mingyang Xia;Cheng Chen;Daimin Xiang;Beifang Ning;Xiuliang Cui;Hengyu Li;Xiaofeng Li;Jin Ding;红阳 王
Second Military Medical University;National Center for Liver Cancer
发表时间:2016-6-1
期 刊:Journal of Hepatology
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=84964355525&partnerID=8YFLogxK
Background & Aims Emerging evidence has demonstrated the aberrant expression of long non-coding RNAs (lncRNAs) in various malignancies including HCC. However, the knowledge of cancer stem cell-related lncRNAs remains limited. Methods lnc-DILC (lncRNA downregulated in liver cancer stem cells (LCSCs)) was identified by microarray and validated by real-time PCR. The role of lnc-DILC in LCSCs was assessed both in vitro and in vivo. Pull down assay and oligoribonucleotides or oligodeoxynucleotides treatment were conducted to evaluate the interaction between lnc-DILC and interleukin-6 (IL-6) promoter. Results Depletion of lnc-DILC markedly enhanced LCSC expansion and facilitated HCC initiation and progression, whereas ectopic expression of lnc-DILC dramatically inhibited LCSC expansion. Mechanistically, lnc-DILC inhibited the autocrine IL-6/STAT3 signaling. The putative binding locus of lnc-DILC within IL-6 promoter was confirmed by pull down assay. Consistently, the oligoribonucleotide mimics and an oligodeoxynucleotide decoy of lnc-DILC abrogated the effects on IL-6 transcription, STAT3 activation and LCSC expansion triggered by lnc-DILC depletion and lnc-DILC overexpression. Moreover, our data suggested that lnc-DILC mediated the crosstalk between TNF-α/NF-κB signaling and IL-6/STAT3 cascade. Clinical investigation demonstrated the reduction of lnc-DILC in patient HCCs, and suggested the correlation between lnc-DILC levels and IL-6, EpCAM or CD24 expression. Decreased lnc-DILC expression in HCCs predicts early recurrence and short survival of patients, highlighting its prognostic value. Conclusions lnc-DILC mediates the crosstalk between TNF-α/NF-κB signaling and autocrine IL-6/STAT3 cascade and connects hepatic inflammation with LCSC expansion, suggesting that lnc-DILC could be not only a potential prognostic biomarker, but also a possible therapeutic target against LCSCs.
医学与生命科学
Scopus度量
年份 | CiteScore | SJR | SNIP |
---|---|---|---|
1996 | |||
1997 | |||
1998 | |||
1999 | 0.984 | 1.428 | |
2000 | 1.219 | 1.307 | |
2001 | 1.469 | 1.493 | |
2002 | 1.489 | 1.55 | |
2003 | 1.569 | 1.795 | |
2004 | 1.544 | 1.417 | |
2005 | 1.577 | 1.504 | |
2006 | 1.931 | 1.638 | |
2007 | 2.141 | 1.677 | |
2008 | 2.309 | 1.7 | |
2009 | 2.317 | 1.866 | |
2010 | 2.927 | 2.141 | |
2011 | 13.5 | 2.819 | 2.378 |
2012 | 13.8 | 3.367 | 2.58 |
2013 | 15.5 | 3.697 | 2.98 |
2014 | 18 | 4.11 | 3.098 |
2015 | 19.6 | 4.686 | 3.438 |
2016 | 19 | 5.012 | 2.929 |
2017 | 22.4 | 5.633 | 3.25 |
2018 | 26.6 | 6.274 | 3.649 |
2019 | 30.3 | 6.817 | 4.641 |
2020 | 32.9 | ||
2021 |
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