The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGF R2) in colon cancer cells
Open accessAbstract
Although microRNA-21 (miR-21) is emerging as an oncogene and has been shown to target several tumor suppressor genes, including programmed cell death 4 (PDCD4), its precise mechanism of action on cancer stem cells (CSCs) is unclear. Herein, we report that FOLFOX-resistant HCT-116 and HT-29 cells that are enriched in CSCs show a 3- to 7-fold upregulation of pre- and mature miR-21 and downregulation of PDCD4. Likewise, overexpression of miR-21 in HCT-116 cells, achieved through stable transfection, led to the downregulation of PDCD4 and transforming growth factor beta receptor 2 (TGFβR2). In contrast, the levels of β-catenin, TCF/LEF activity and the expression of c-Myc, Cyclin-D, which are increased in CSCs, are also augmented in miR-21 overexpressing colon cancer cells, accompanied by an increased sphere forming ability in vitro and tumor formation in SCID mice. Downregulation of TGFβR2 could be attributed to decreased expression of the receptor as evidenced by reduction in the activity of the luciferase gene construct comprising TGFβR2-3' untranslated region (UTR) sequence that binds to miR-21. Moreover, we observed that downregulation of miR-21 enhances luciferase-TGFβR2-3' UTR activity suggesting TGFβR2 as being one of the direct targets of miR-21. Further support is provided by the observation that transfection of TGFβR2 in HCT-116 cells attenuates TCF/LEF luciferase activity, accompanied by decreased expression of β-catenin, c-Myc and Cyclin-D1. Our current data suggest that miR-21 plays an important role in regulating stemness by modulating TGFβR2 signaling in colon cancer cells.
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Cites
Tumour stem cells and drug resistance
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SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
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miR‐21: a small multi‐faceted RNA
Krichevsky, A. M., & Gabriely, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00556.x · Cited by 987
OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma
Medina, P. P., Nolde, M., & Slack, F. J. (2010) · Nature · doi:10.1038/nature09284 · Cited by 971
MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators
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MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene
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Ishitani, T., Ninomiya-Tsuji, J., Nagai, S.-I., Nishita, M., Meneghini, M., Barker, N., Waterman, M., Bowerman, B., Clevers, H., Shibuya, H., et al. (1999) · Nature · doi:10.1038/21674 · Cited by 621
Cited by
Emerging role of microRNA-21 in cancer
Feng, Y.-H., & Tsao, C.-J. (2016) · Biomedical Reports · doi:10.3892/br.2016.747 · Cited by 454
Olivieri, F., Spazzafumo, L., Santini, G., Lazzarini, R., Albertini, M. C., Rippo, M. R., Galeazzi, R., Abbatecola, A. M., Marcheselli, F., Monti, D., et al. (2012) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.09.004 · Cited by 248
The Roles of Cancer Stem Cells and Therapy Resistance in Colorectal Carcinoma
Das, P. K., Islam, F., & Lam, A. K. (2020) · Cells · doi:10.3390/cells9061392 · Cited by 210
The crosstalk between microRNAs and the Wnt/β-catenin signaling pathway in cancer
Peng, Y., Zhang, X., Feng, X., Fan, X., & Jin, Z. (2017) · Oncotarget · doi:10.18632/oncotarget.12923 · Cited by 149
MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology
Chawra, H. S., Agarwal, M., Mishra, A., Chandel, S. S., Singh, R. P., Dubey, G., Kukreti, N., & Singh, M. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155091 · Cited by 91
Metadata
- Authors
- Yu, Y., Kanwar, S. S., Patel, B. B., Oh, P.-S., Nautiyal, J., Sarkar, F. H., & Majumdar, A. P. N.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-11-09
- Volume
- 33
- Issue
- 1
- Pages
- 68-76
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2115590702
- Cited by
- 258
- References
- 9
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- bronze
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