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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Journal of Experimental & Clinical Cancer Research 1/2018

The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2018
Autoren:
Leilei Zhang, Xiaoyu He, Fang Li, Hui Pan, Xiaolin Huang, Xuyang Wen, He Zhang, Bin Li, Shengfang Ge, Xiaofang Xu, Renbing Jia, Xianqun Fan
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s13046-018-0679-5) contains supplementary material, which is available to authorized users.
Leilei Zhang, Xiaoyu He and Fang Li contributed equally to this report.
Xiaofang Xu, Renbing Jia and Xianqun Fan are senior authors of this report.

Abstract

Background

MicroRNAs (miRNAs) have been shown to function in many different cellular processes, including proliferation, apoptosis, differentiation and development. miR-181a, -181b, -181c and -181d are miR-181 members of the family, which has been rarely studied, especially uveal melanoma.

Methods

The expression level of miR-181 family in human uveal melanoma cell lines was measured via real-time PCR (RT-PCR). The function of miR-181 on cell cycle was detected through Flow Cytometry assay. Microarray assay and Bioinformatics analysis were used to find the potential target of miR-181b, and dual-luciferase reporter assays further identified the target gene.

Results

MiR-181 family members were found to be highly homologous across different species and their upregulation significantly induces UM cell cycle progression. Of the family members, miR-181b was significantly overexpressed in UM tissues and most UM cells. Bioinformatics and dual luciferase reporter assay confirmed CTDSPL as a target of miR-181b. miR-181b over-expression inhibited CTDSPL expression, which in turn led to the phosphorylation of RB and an accumulation of the downstream cell cycle effector E2F1, promoting cell cycle progression in UM cells. Knockdown CTDSPL using siRNAs showing the same effect, including increase of E2F1 and the progression of cell cycle.

Conclusions

MiR-181 family members are key negative regulators of CTDSPL-mediated cell cycle progression. These results highlight that miR-181 family members, especially miR-181b, may be useful in the development of miRNA-based therapies and may serve as novel diagnostic and therapeutic candidate for UM.
Zusatzmaterial
Additional file 1: There are no interactions between CTDSPL and RB1, cyclins and CTDSPL. (TIF 9130 kb)
13046_2018_679_MOESM1_ESM.tif
Literatur
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