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J Exp Clin Cancer Res. 2018 Jan 30;37(1):15. doi: 10.1186/s13046-018-0679-5.

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

Zhang L1,2, He X1,2, Li F1,2, Pan H1,2, Huang X1,2, Wen X1,2, Zhang H1,2, Li B3, Ge S1,2, Xu X4,5, Jia R6,7, Fan X8,9.

Author information

1
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
2
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
3
Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.
4
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. xuxu0139@hotmail.com.
5
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. xuxu0139@hotmail.com.
6
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. jrb19760517@hotmail.com.
7
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. jrb19760517@hotmail.com.
8
Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. fanxq@sjtu.edu.cn.
9
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. fanxq@sjtu.edu.cn.

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.

KEYWORDS:

CTDSPL; Cell cycle; E2F1; Uveal melanoma; miR-181

PMID:
29382357
PMCID:
PMC5791374
DOI:
10.1186/s13046-018-0679-5
[Indexed for MEDLINE]
Free PMC Article

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