SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma

被引：126

作者：

Xu, Yi ^{[1
]}

Yao, Yue ^{[2
]}

Jiang, Xingming ^{[1
]}

Zhong, Xiangyu ^{[1
]}

Wang, Zhidong ^{[1
]}

Li, Chunlong ^{[1
]}

Kang, Pengcheng ^{[1
]}

Leng, Kaiming ^{[1
]}

Ji, Daolin ^{[1
]}

Li, Zhenglong ^{[1
]}

Huang, Lining ^{[1
]}

Qin, Wei ^{[1
]}

Cui, Yunfu ^{[1
]}

机构：

[1] Harbin Med Univ, Affiliated Hosp 2, Dept Hepatopancreatobiliary Surg, Harbin 150086, Heilongjiang, Peoples R China

[2] Harbin Med Univ, Affiliated Hosp 2, Dept Endocrinol & Metab, Harbin 150086, Heilongjiang, Peoples R China

来源：

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 2018年 / 37卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Cholangiocarcinoma; lncRNA; SPRY4-IT1; Scaffold; Oncogenic properties; LONG NONCODING RNA; HUMAN BREAST-CANCER; CELL LUNG-CANCER; GASTRIC-CANCER; PROMOTES PROLIFERATION; DOWN-REGULATION; POOR-PROGNOSIS; EXPRESSION; INVASION; GROWTH;

D O I：

10.1186/s13046-018-0747-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Accumulating evidence has indicated that long non-coding RNAs (lncRNAs) behave as a novel class of transcription products during multiple cancer processes. However, the mechanisms responsible for their alteration in cholangiocarcinoma (CCA) are not fully understood. Methods: The expression of SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the association between SPRY4-IT1 transcription and clinicopathologic features was analyzed. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of SPRY4-IT1 and activate its transcription. The biological function of SPRY4-IT1 in CCA cells was evaluated both in vitro and in vivo. ChIP, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were performed to determine the molecular mechanism of SPRY4-IT1 in cell proliferation, apoptosis and invasion. Results: SPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p. Conclusions: Our data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA.

引用

页数：13

共 41 条

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