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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes
Jie He1, Jiangbin Wu, Naihan Xu
1School of Life Sciences, Tsinghua University, Beijing 100084, PR China.
Abstract:
MiR-210 is up-regulated in multiple cancer types but its function is disputable and further investigation is necessary. Using a bioinformatics approach, we identified the putative target genes of miR-210 in hypoxia-induced CNE cells from genome-wide scale. Two functional gene groups related to cell cycle and RNA processing were recognized as the major targets of miR-210. Here, we investigated the molecular mechanism and biological consequence of miR-210 in cell cycle regulation, particularly mitosis. Hypoxia-induced up-regulation of miR-210 was highly correlated with the down-regulation of a group of mitosis-related genes, including Plk1, Cdc25B, Cyclin F, Bub1B and Fam83D. MiR-210 suppressed the expression of these genes by directly targeting their 3'-UTRs. Over-expression of exogenous miR-210 disturbed mitotic progression and caused aberrant mitosis. Furthermore, miR-210 mimic with pharmacological doses reduced tumor formation in a mouse metastatic tumor model. Taken together, these results implicate that miR-210 disturbs mitosis through targeting multi-genes involved in mitotic progression, which may contribute to its inhibitory role on tumor formation.
Insights
MicroRNA-210 (miR-210) disrupts mitosis by targeting key cell cycle genes. This finding suggests miR-210 may inhibit tumor formation, offering potential therapeutic insights.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- MicroRNA-210 (miR-210) is frequently upregulated in various cancers.
- The precise function of miR-210 in cancer remains unclear and requires further investigation.
Purpose of the Study:
- To elucidate the molecular mechanisms and biological consequences of miR-210 in cell cycle regulation, specifically focusing on mitosis.
- To identify and validate miR-210 target genes involved in mitotic progression.
Main Methods:
- Bioinformatic analysis to identify putative miR-210 target genes in hypoxia-induced CNE cells.
- Experimental validation of miR-210 targeting of specific mitosis-related genes (Plk1, Cdc25B, Cyclin F, Bub1B, Fam83D) via their 3'-UTRs.
- Assessment of miR-210's impact on mitotic progression and tumor formation in a mouse model.
Main Results:
- Two major functional gene groups, cell cycle and RNA processing, were identified as miR-210 targets.
- Hypoxia-induced miR-210 upregulation correlated with downregulation of several key mitosis genes.
- Overexpression of miR-210 led to disturbed mitotic progression and aberrant mitosis.
- Administration of miR-210 mimic reduced tumor formation in a metastatic mouse model.
Conclusions:
- MiR-210 disrupts mitosis by directly targeting multiple genes crucial for mitotic progression.
- These findings highlight a potential inhibitory role of miR-210 in tumor formation, suggesting its therapeutic relevance.
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