MicroRNA-21 targets tumor suppressor genes in invasion and metastasis
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.
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This analysis confirmed regulation of tropomyosin 1 (TPM1) by miR-21, previously reported in MCF7 cells.
“Our analysis also confirmed tropomyosin 1 (TPM1) regulation by miR-21, previously reported to occur in MCF7 cells (59, 60).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [60]
Knock-down of miR-21 in the metastatic breast cancer MD-MBA-231 cells reduced invasion and metastasis.
“Knock-down of miR-21 in the metastatic breast cancer MD-MBA-231 cells reduced invasion and metastasis (Zhu et al., 2008).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Zhu et al., 2008
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Regulation of tumor suppressor PDCD4 by novel protein kinase C isoforms
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- Authors
- Zhu, S., Wu, H., Wu, F., Nie, D., Sheng, S., & Mo, Y.-Y.
- Affiliations
- SIU Medicine (US)
- Wayne State University (US)
- Corresponding author
- Mo, Yin-Yuan
- Venue
- Cell Research
- Published
- 2008-02-12
- Volume
- 18
- Issue
- 3
- Pages
- 350-359
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- OpenAlex
- W1972892962
- Cited by
- 1,051
- References
- 5
- Citations by year
- 2026: 21 · 2025: 26 · 2024: 35 · 2023: 28 · 2022: 33 · 2021: 35 · 2020: 44 · 2019: 43 · 2018: 47 · 2017: 51 · 2016: 58 · 2015: 82 · 2014: 74 · 2013: 95 · 2012: 89
- FWCI
- 32.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Cancer Institute (R01CA102630, CA84176, CA 102630, R01CA084176)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- miR-21, tumor suppressor, cell invasion, metastasis, breast cancer, TPM1, PDCD4, maspin, post-transcriptional regulation, MDA-MB-231 cells, lung metastasis, cell migration
- MeSH terms
- Animals, Breast Neoplasms, Female, Humans, Lung Neoplasms, Male, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Oncogenes, RNA, Messenger, Tropomyosin, Serpins, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, Tumor Suppressor Proteins, MicroRNAs, Cell Line, Tumor, Apoptosis Regulatory Proteins, Mice
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