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Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-21 targets tumor suppressor genes in invasion and metastasis
Shuomin Zhu1, Hailong Wu, Fangting Wu
1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 825 N. Rutledge, PO Box 19626, Springfield, IL 62794, USA.
Abstract:
MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 (TPM1). Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 (PDCD4) and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.
Insights
MicroRNA-21 (miR-21) promotes breast cancer metastasis by targeting tumor suppressor genes like TPM1, PDCD4, and maspin. Suppressing miR-21 significantly reduced cancer invasion and metastasis, suggesting it as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression post-transcriptionally.
- Previous research indicated miR-21 acts as an oncogene in tumorigenesis, partly via regulating the tumor suppressor tropomyosin 1 (TPM1).
- TPM1 is known to influence cell migration, prompting further investigation into miR-21's role in invasion and metastasis.
Purpose of the Study:
- To investigate the role of miR-21 in cell invasion and tumor metastasis.
- To identify additional targets of miR-21 involved in these processes.
- To evaluate the therapeutic potential of targeting miR-21 in advanced cancers.
Main Methods:
- Suppression of miR-21 in metastatic breast cancer MDA-MB-231 cells.
- Ectopic expression of TPM1 in MDA-MB-231 cells.
- Identification and validation of miR-21 targets (PDCD4, maspin).
- Analysis of gene expression correlation in human breast tumor specimens.
Main Results:
- Suppression of miR-21 significantly reduced invasion and lung metastasis in a breast cancer model.
- Ectopic expression of TPM1, PDCD4, and maspin inhibited cell invasion.
- PDCD4 and maspin were identified as direct targets of miR-21.
- Inverse correlation observed between miR-21 expression and PDCD4/maspin levels in human breast tumors.
Conclusions:
- Oncogenic miR-21 contributes to tumor invasion and metastasis by targeting multiple tumor suppressor genes, including TPM1, PDCD4, and maspin.
- miR-21 plays a role beyond tumor growth, impacting invasive and metastatic capabilities.
- Targeting miR-21 presents a potential novel therapeutic strategy for advanced cancers.
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