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NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells.

Abstract：

:Accumulating evidence has highlighted the potential role of non-coding RNAs (ncRNAs) and upstream open-reading frames (uORFs) in the biological behaviors of glioblastoma. Here, we elucidated the function and possible molecular mechanisms of the effect of some ncRNAs and NR2C2-uORF on the biological behaviors of gliomas. Quantitative real-time PCR was conducted to profile the cell expression of lnc-UCA1 and microRNA-627-5p (miR-627-5p) in glioma tissues and cells. Western blot assay was used to determine the expression levels of NR2C2, SPOCK1, and NR2C2-uORF in glioma tissues and cells. Stable knockdown of lnc-UCA1 or overexpression of miR-627-5p in glioma cell lines (U87 and U251) were established to explore the function of lnc-UCA1 and miR-627-5p in glioma cells. Further, Dual luciferase report assay was used to investigate the correlation between lnc-UCA1 and miR-627-5p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate lnc-UCA1 and miR-627-5p function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between NR2C2 and SPOCK1 as well as NR2C2 between lnc-UCA1. This study confirmed that lnc-UCA1 was up-regulated in glioma tissues and cells. UCA1 knockdown inhibited the malignancies of glioma cells by reducing proliferation, migration, and invasion, but inducing apoptosis. We found that lnc-UCA1 acted as miR-627-5p sponge in a sequence-specific manner. Meanwhile, upregulated lnc-UCA1 inhibited miR-627-5p expression. In addition, miR-627-5p targeted 3'UTR of NR2C2 and down-regulated its expression. Moreover, UCA1 knockdown impaired NR2C2 expression by upregulating miR-627-5p. An uORF was identified in mRNA 5'UTR of NR2C2 and overexpression of whom negatively regulated NR2C2 expression. Remarkably, lnc-UCA1 knockdown combined with uORF overepression and NR2C2 knockdown led to severe tumor suppression in vivo. This study demonstrated that the NR2C2-uORF impaired the pivotal roles that UCA1-miR-627-5p-NR2C2 feedback loop had in regulating the malignancies of glioma cells by targeting NR2C2 directly. And this may provide a potential therapeutic strategy for treating glioma.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Fan Z,Zheng J,Xue Y,Liu X,Wang D,Yang C,Ma J,Liu L,Ruan X,Wang Z,Liu Y

doi

10.1038/s41419-018-1149-x

subject

Has Abstract

pub_date

2018-12-05 00:00:00

pages

1165

issue

issn

2041-4889

pii

10.1038/s41419-018-1149-x

journal_volume

pub_type

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NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells.