MicroRNA-21 Targets the Tumor Suppressor Gene Tropomyosin 1 (TPM1)
Open accessAbstract
MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that mir-21 is overexpressed in tumor tissues compared with the matched normal tissues. Moreover, suppression of mir-21 by antisense oligonucleotides inhibits tumor cell growth both in vitro and in vivo. However, it remains largely unclear as to how mir-21 affects tumor growth, because our understanding of mir-21 targets is limited. In this study, we performed two-dimensional differentiation in-gel electrophoresis of tumors treated with anti-mir-21 and identified the tumor suppressor tropomyosin 1 (TPM1) as a potential mir-21 target. In agreement with this, there is a putative mir-21 binding site at the 3'-untranslated region (3'-UTR) of TPM1 variants V1 and V5. Thus, we cloned the 3'-UTR of TPM1 into a luciferase reporter and found that although mir-21 down-regulated the luciferase activity, anti-mir-21 up-regulated it. Moreover, deletion of the mir-21 binding site abolished the effect of mir-21 on the luciferase activity, suggesting that this mir-21 binding site is critical. Western blot with the cloned TPM1-V1 plus the 3'-UTR indicated that TPM1 protein level was also regulated by mir-21, whereas real-time quantitative reverse transcription-PCR revealed no difference at the mRNA level, suggesting translational regulation. Finally, overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth. Thus, down-regulation of TPM1 by mir-21 may explain, at least in part, why suppression of mir-21 can inhibit tumor growth, further supporting the notion that mir-21 functions as an oncogene.
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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 [59]
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Silencing of microRNAs in vivo with ‘antagomirs’
Krützfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., & Stoffel, M. (2005) · Nature · doi:10.1038/nature04303 · Cited by 3,949 · see citing works
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Research works printed but not linked: 5
- Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., Rassenti, L., Kipps, T., Negrini, M., Bullrich, F., and Croce, C. M. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 15524 -15529
- Si, M. L., Zhu, S., Wu, H., Lu, Z., Wu, F., and Mo, Y. Y. (2006) Oncogene, in press
- Boyd, J., Risinger, J. I., Wiseman, R. W., Merrick, B. A., Selkirk, J. K., and Barrett, J. C. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11534 -11538
- Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C. G., Kipps, T. J., Negrini, M., and Croce, C. M. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 13944 -13949
- Prasad, G. L., Fuldner, R. A., and Cooper, H. L. (1993) Proc. Natl. Acad. Sci.
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Gabriely, G., Wurdinger, T., Kesari, S., Esau, C. C., Burchard, J., Linsley, P. S., & Krichevsky, A. M. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00479-08 · Cited by 888 · see citing works
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Markou, A., Tsaroucha, E. G., Kaklamanis, L., Fotinou, M., Georgoulias, V., & Lianidou, E. S. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2007.101741 · Cited by 441 · see citing works
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Ohlsson Teague, E. M. C., Print, C. G., & Hull, M. L. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmp034 · Cited by 309 · see citing works
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Jenike, A. E., & Halushka, M. K. (2021) · Biomarker Research · doi:10.1186/s40364-021-00272-1 · Cited by 248 · see citing works
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Chen, Y., Liu, W., Chao, T., Zhang, Y., Yan, X., Gong, Y., Qiang, B., Yuan, J., Sun, M., & Peng, X. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.06.034 · Cited by 217 · see citing works
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Huang, T.-H., Wu, F., Loeb, G. B., Hsu, R., Heidersbach, A., Brincat, A., Horiuchi, D., Lebbink, R. J., Mo, Y.-Y., Goga, A., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.006676 · Cited by 191 · see citing works
Self-citationRegulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma
Liu, M., Wu, H., Liu, T., Li, Y., Wang, F., Wan, H., Li, X., & Tang, H. (2009) · Cell Research · doi:10.1038/cr.2009.72 · Cited by 189 · see citing works
Self-citationDownregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo
Gaur, A. B., Holbeck, S. L., Colburn, N. H., & Israel, M. A. (2011) · Neuro-Oncology · doi:10.1093/neuonc/nor033 · Cited by 180 · see citing works
Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform
Rajan, S., Jagatheesan, G., Karam, C. N., Alves, M. L., Bodi, I., Schwartz, A., Bulcao, C. F., D'Souza, K. M., Akhter, S. A., Boivin, G. P., et al. (2010) · Circulation · doi:10.1161/circulationaha.109.889725 · Cited by 92 · see citing works
Costa, P. M., Cardoso, A. L., Nóbrega, C., Pereira de Almeida, L. F., Bruce, J. N., Canoll, P., & Pedroso de Lima, M. C. (2013) · Human Molecular Genetics · doi:10.1093/hmg/dds496 · Cited by 80 · see citing works
Targeting miR-21 in glioma: a small RNA with big potential
Moore, L. M., & Zhang, W. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.527334 · Cited by 51 · see citing works
Yu, Y., Yao, Y., Yan, H., Wang, R., Zhang, Z., Sun, X., Zhao, L., Ao, X., Xie, Z., & Wu, Q. (2016) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2016.28 · Cited by 31 · see citing works
- Authors
- Zhu, S., Si, M.-L., Wu, H., & Mo, Y.-Y.
- Affiliations
- SIU Medicine (US)
- Corresponding author
- Mo, Yin-Yuan
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 282
- Issue
- 19
- Pages
- 14328-14336
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2008955962
- Cited by
- 1,090
- References
- 1
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 25 · 2023: 20 · 2022: 29 · 2021: 32 · 2020: 34 · 2019: 31 · 2018: 35 · 2017: 45 · 2016: 56 · 2015: 75 · 2014: 80 · 2013: 76 · 2012: 93
- FWCI
- 38.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- National Cancer Institute (R01CA102630, CA 102630)
- 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
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- miR-21, TPM1, microRNA target regulation, 3' untranslated region, translational regulation, tumor suppressor, oncogenes, breast cancer, MCF-7 cells, anchorage-independent growth, antisense oligonucleotides
- MeSH terms
- Animals, Breast Neoplasms, Cell Adhesion, Female, Humans, Luciferases, Mice, Nude, RNA Processing, Post-Transcriptional, RNA, Messenger, Tropomyosin, Tumor Stem Cell Assay, Gene Expression Regulation, Neoplastic, Oligonucleotides, Antisense, 3' Untranslated Regions, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice
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