1. The miR-181 family promotes cell cycle by targeting CTDSPL, a phosphatase-like tumor suppressor in uveal melanoma
- Author
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Hui Pan, Xiaolin Huang, Xiaoyu He, Xiaofang Xu, Shengfang Ge, Fang Li, Renbing Jia, He Zhang, Xuyang Wen, Xianqun Fan, Leilei Zhang, and Bin Li
- Subjects
0301 basic medicine ,Uveal Neoplasms ,Cancer Research ,Small interfering RNA ,Apoptosis ,Biology ,lcsh:RC254-282 ,Models, Biological ,Flow cytometry ,03 medical and health sciences ,0302 clinical medicine ,Uveal melanoma ,Downregulation and upregulation ,Cell Line, Tumor ,microRNA ,medicine ,E2F1 ,Humans ,Genes, Tumor Suppressor ,3' Untranslated Regions ,Melanoma ,Conserved Sequence ,Cell Proliferation ,Gene knockdown ,medicine.diagnostic_test ,Research ,Gene Expression Profiling ,Tumor Suppressor Proteins ,Cell Cycle ,Computational Biology ,Cell cycle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,CTDSPL ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,miR-181 ,030220 oncology & carcinogenesis ,Multigene Family ,Cancer research ,RNA Interference - 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. Electronic supplementary material The online version of this article (10.1186/s13046-018-0679-5) contains supplementary material, which is available to authorized users.
- Published
- 2018