登录  注册
消化病学学术中心首页 > 期刊 > 中国作者重要发表

消化病学学术中心

长链非编码RNA-DILC可通过IL-6/STAT3轴调节肝癌干细胞

Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis

来源:Scopus 发布时间:2016-7-8
作者:Wang X, Sun W, Shen W, Xia M, Chen C, Xiang D1, Ning B, Cui X, Li H, Li X, Ding J, Wang H.
机构: 第二军医大学东方肝胆外科医院国际合作生物信号转导研究中心
期刊: J HEPATOL 2016年6月6期64卷

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. © 2016 European Association for the Study of the Liver.

通讯作者:The International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438 Shanghai, China.
顶一下(0

发表评论

学科影响因子排名more

 会议回顾 more

  • “2016 消化中外盛举 Best...

  • AASLD The Liver M...

  • 【专题】2015年美国消化疾病周(...

 热门病例 more

 热门指南  more

Elsevier中国网站
爱唯医学网
爱思唯尔科技部
NursingChina
柳叶刀中文版
大通医疗决策
医大爱思唯尔
Elsevier医学数据库
CK
Journal Consult
Procedures_CONSULT
ClinicalPharmacologyLogo
3D Interact Anatomy
Mosby’s Nursing Consult
NursingChina
Science Direct