Open AccessLong non‐coding RNA LOC 554202 modulates chordoma cell proliferation and invasion by recruiting EZH 2 and regulating miR‐31 expression
Author(s) -
Ma Xianli,
Qi Shengjin,
Duan Zhenying,
Liao Hongzhan,
Yang Baohua,
Wang Wenbo,
Tan Jie,
Li Qinghua,
Xia Xuewei
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12388
Subject(s) - chordoma , gene knockdown , biology , rna , cell growth , competing endogenous rna , cancer research , cell culture , microrna , reporter gene , transfection , microbiology and biotechnology , apoptosis , gene expression , gene , long non coding rna , pathology , medicine , genetics
Objectives Chordoma is a rare malignant bone tumour arising from notochordal remnants. Long non‐coding RNA LOC 554202, as the host gene of miR‐31, contributes to various cancer developments. However, little is known about the biological function of LOC 554202 in chordoma. Here, the relationship between Lnc RNA LOC 554202, miR‐31 and EZH 2 was elucidated in chordoma. Materials and methods The levels of LOC 554402, miR‐31, EZH 2, RNF 144B, and epithelial‐mesenchymal transition ( EMT ) markers were measured in chordoma tissues and the chordoma cell lines via quantitative real‐time PCR ( qRT ‐ PCR ) or Western blot. FISH assay demonstrated the LOC 554402 expression in chordoma tissues. The chordoma cell lines, U‐ CH 1 and JHC 7, were transfected with si RNA or mi RNA mimics and analysed for cell proliferation ability, apoptosis, cell migration, and invasion. RNA pull down, RIP assay, and Luciferase Reporter Assay were used to analyze the interaction between LOC 554202 and EZH 2. Animal tumour xenografts were generated, and qRT ‐ PCR was performed to investigate EZH 2, miR‐31, and RNB 144B expression on tumour growth in vivo. Results We found elevated expression of LOC 554202 was associated with a decreased level of miR‐31 in cancer tissues. Knockdown of LOC 554202 or overexpression of miR‐31 suppressed the proliferation, migration, and invasion of chordoma cells. Unexpectedly, EZH 2 as a binding protein of LOC 554202, and it was positively regulated by LOC 554202, leading to the reduced expression of miR‐31. Furthermore, the impaired function of miR‐31 restored expression of the oncogene RNF 144B and maintained the metastasis‐promoting activity in vitro. The results in vivo confirmed the anti‐tumour effects of knockdown of LOC 554202, which inhibited EZH 2/miR‐31 to activate the oncogene RNF 144B. Conclusion Our results suggest that LOC 554202 may play an important role in the progression of chordoma by the direct upregulation of EZH 2 and indirect promotion of RNF 144B via miR‐31.