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Updated: Jun 1, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis
Xiaodong Ma1, Munish Kumar, Saibyasachi N Choudhury
1Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville, 319 Abraham Flexner Way, Louisville, KY 40202, USA.
Abstract:
MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies. To determine whether miR-21 promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In response to the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, miR-21-null mice showed a significant reduction in papilloma formation compared with wild-type mice. We revealed that cellular apoptosis was elevated and cell proliferation was decreased in mice deficient of miR-21 compared to wild-type animals. In addition, we found that a large number of validated or predicted miR-21 target genes were up-regulated in miR-21-null keratinocytes, which are precursor cells to skin papillomas. Specifically, up-regulation of Spry1, Pten, and Pdcd4 when miR-21 was ablated coincided with reduced phosphorylation of ERK, AKT, and JNK, three major downstream effectors of Ras activation that plays a predominant role in DMBA-initiated skin carcinogenesis. These results provide in vivo evidence that miR-21 exerts its oncogenic function through negatively regulating its target genes.
Insights
MicroRNA 21 (miR-21) drives cancer development. Deleting the miR-21 gene in mice significantly reduced skin tumors by increasing cell death and decreasing cell growth, confirming its oncogenic role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA 21 (miR-21) is frequently overexpressed in various cancers, suggesting a role in tumorigenesis.
- Its specific function in promoting tumor development in vivo remains to be fully elucidated.
Purpose of the Study:
- To investigate the in vivo role of miR-21 in chemical-induced skin carcinogenesis.
- To determine if miR-21 promotes tumor development by regulating target genes involved in cell proliferation and apoptosis.
Main Methods:
- Generation of miR-21-null mice by gene knockout.
- Application of the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate skin carcinogenesis protocol.
- Analysis of papilloma formation, cellular apoptosis, cell proliferation, and expression of miR-21 target genes and signaling pathways (ERK, AKT, JNK).
Main Results:
- miR-21-null mice exhibited significantly reduced papilloma formation compared to wild-type mice.
- Absence of miR-21 led to increased cellular apoptosis and decreased cell proliferation in the skin.
- Key miR-21 target genes (Spry1, Pten, Pdcd4) were upregulated in miR-21-null keratinocytes, correlating with reduced phosphorylation of ERK, AKT, and JNK signaling pathways.
Conclusions:
- These findings provide in vivo evidence that miR-21 promotes skin carcinogenesis.
- miR-21 exerts its oncogenic function by negatively regulating its target genes, impacting critical signaling pathways involved in cell growth and survival.
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