CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer

被引：845

作者：

Wang, Jiayi ^{[1
]}

Liu, Xiangfan ^{[1
,2
]}

Wu, Huacheng ^{[3
]}

Ni, Peihua ^{[2
]}

Gu, Zhidong ^{[1
]}

Qiao, Yongxia ^{[4
]}

Chen, Ning ^{[2
]}

Sun, Fenyong ^{[5
]}

Fan, Qishi ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Lab Med, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Fac Med Lab Sci, Shanghai 200025, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pathol, Shanghai 200025, Peoples R China

[4] Tongji Univ, Dept Prevent Med, Shanghai 200092, Peoples R China

[5] Jinan Univ, Coll Life Sci & Technol, Inst Bioengn, Guangzhou 510632, Guangdong, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2010年 / 38卷 / 16期

基金：

美国国家科学基金会; 上海市自然科学基金;

关键词：

TRANSCRIPTIONAL ACTIVATION; IDENTIFICATION; PROMOTER; GENE; PHOSPHORYLATION; TARGET; ROLES; PKA;

D O I：

10.1093/nar/gkq285

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Long non-coding RNA (lncRNA), highly up-regulated in liver cancer (HULC) plays an important role in tumorigenesis. Depletion of HULC resulted in a significant deregulation of several genes involved in liver cancer. Although up-regulation of HULC expression in hepatocellular carcinoma has been reported, the molecular mechanisms remain unknown. In this study, we used in vivo and in vitro approaches to characterize cancer-dependent alterations in the chromatin organization and find a CREB binding site (encompassing from -67 to -53 nt) in the core promoter. Besides, we also provided evidence that PKA pathway may involved in up-regulation of HULC. Furthermore, we demonstrated HULC may act as an endogenous 'sponge', which down-regulates a series of microRNAs (miRNAs) activities, including miR-372. Inhibition of miR-372 leads to reducing translational repression of its target gene, PRKACB, which in turn induces phosphorylation of CREB. Over-expression of miR-372 decreases the association of CREB with the proximal promoter, followed by the dissociation of P300, resulting in a change of the histone 'code', such as in deacetylation and methylation. The study elucidates that fine tuning of HULC expression is part of an auto-regulatory loop in which it's inhibitory to expression and activity of miR-372 allows lncRNA up-regulated expression in liver cancer.

引用

页码：5366 / 5383

页数：18

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