MicroRNA-224 sustains Wnt/β-catenin signaling and promotes aggressive phenotype of colorectal cancer
Open accessAbstract
Background: Growing evidence suggests that Wnt/β-catenin pathway plays an important role in CRC development, progression and metastasis. Aberrant miR-224 expression has been reported in CRC. However, the mechanism of miR-224 promotes both proliferation and metastatic ability largely remains unclear. Methods: Real-time PCR was used to quantify miR-224 expression. Luciferase reporter assays were conducted to confirm the activity of Wnt/β-catenin pathway and target gene associations, and immunofluorescence staining assay was performed to observe the nuclear translocation of β-catenin. Bioinformatics analysis combined with in vivo and vitro functional assays showed the potential target genes, GSK3β and SFRP2, of miR-224. Specimens from forty patients with CRC were analyzed for the expression of miR-224 and the relationship with GSK3β/SFRP2 by real-time PCR and western blot. Results: Bioinformatics and cell luciferase function studies verified the direct regulation of miR-224 on the 3’-UTR of the GSK3β and SFRP2 genes, which leads to the activation of Wnt/β-catenin signaling and the nuclear translocation of β-catenin. In addition, knockdown of miR-224 significantly recovered the expression of GSK3β and SFRP2 and attenuated Wnt/β-catenin-mediated cell metastasis and proliferation. The ectopic upregulation of miR-224 dramatically inhibited the expression of GSK3β/SFRP2 and enhanced CRC proliferation and invasion. Conclusion: Our research showed mechanistic links between miR-224 and Wnt/β-catenin in the pathogenesis of CRC through modulation of GSK3β and SFRP2.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
miRNA-224 is associated with activation of Wnt/β-catenin signaling through inhibition of GSK3β and SFRP2 expression.
“miRNA-224, which is also up-regulated in hEDS/HSD cells, is associated with the activation of the Wnt/β-catenin signaling through the inhibition of the expression of glycogen synthase kinase 3β and SFRP2, which are known Wnt suppressors [169].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [169]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A genetic model for colorectal tumorigenesis
Fearon, E. R., & Vogelstein, B. (1990) · Cell · doi:10.1016/0092-8674(90)90186-i · Cited by 12,132 · see citing works
Siegel, R., Naishadham, D., & Jemal, A. (2013) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21166 · Cited by 11,825 · see citing works
MicroRNA signatures in human cancers
Calin, G. A., & Croce, C. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1997 · Cited by 7,592 · see citing works
Identification of c- <i>MYC</i> as a Target of the APC Pathway
He, T.-C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., & Kinzler, K. W. (1998) · Science · doi:10.1126/science.281.5382.1509 · Cited by 4,566 · see citing works
β-Catenin regulates expression of cyclin D1 in colon carcinoma cells
Tetsu, O., & McCormick, F. (1999) · Nature · doi:10.1038/18884 · Cited by 3,601 · see citing works
Secreted antagonists of the Wnt signalling pathway
Kawano, Y., & Kypta, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00623 · Cited by 1,584 · see citing works
A new member of the frizzled family from Drosophila functions as a Wingless receptor
Bhanot, P., van den Brink, M. R. M., Samos, C. H., Hsieh, J.-C., Wang, Y., Macke, J. P., Andrew, D. J., Nathans, J., & Nusse, R. (1996) · Nature · doi:10.1038/382225a0 · Cited by 1,504 · see citing works
Brabletz, T., Jung, A., Reu, S., Porzner, M., Hlubek, F., Kunz‐Schughart, L. A., Knuechel, R., & Kirchner, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171610498 · Cited by 1,048 · see citing works
Wnt Signaling Requires Sequestration of Glycogen Synthase Kinase 3 inside Multivesicular Endosomes
Taelman, V. F., Dobrowolski, R., Plouhinec, J.-L., Fuentealba, L. C., Vorwald, P. P., Gumper, I., Sabatini, D. D., & Robertis, E. M. D. (2010) · Cell · doi:10.1016/j.cell.2010.11.034 · Cited by 715 · see citing works
Dow, L. E., O’Rourke, K. P., Simon, J. M., Tschaharganeh, D. F., van Es, J. H., Clevers, H. C., & Lowe, S. W. (2015) · Cell · doi:10.1016/j.cell.2015.05.033 · Cited by 549 · see citing works
The genetics of hereditary colon cancerPreprint
Rustgi, A. K. (2007) · Genes & Development · doi:10.1101/gad.1593107 · Cited by 528 · see citing works
Song, S. J., Poliseno, L., Song, M. S., Ala, U., Webster, K. A., Ng, C., Beringer, G., Brikbak, N. J., Yuan, X., Cantley, L. C., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.026 · Cited by 491 · see citing works
Diversity of LEF/TCF action in development and disease
Arce, L., Yokoyama, N. N., & Waterman, M. L. (2006) · Oncogene · doi:10.1038/sj.onc.1210056 · Cited by 439 · see citing works
Wang, Y., Lee, A. T. C., Ma, J. Z.-I., Wang, J., Ren, J., Yang, Y., Tantoso, E., Li, K.-B., Ooi, L. L., Tan, P. B. O., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m707629200 · Cited by 365 · see citing works
MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis
Cai, J., Guan, H., Fang, L., Yang, Y., Zhu, X., Yuan, J., Wu, J., & Li, M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65871 · Cited by 331 · see citing works
Self-citationSong, L.-B., Zeng, M., Liao, W., Zhang, L., Mo, H., Liu, W.-L., Shao, J., Wu, Q., Li, M.-Z., Xia, Y.-F., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0094 · Cited by 328 · see citing works
Self-citationMicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells
Hwang, W., Jiang, J., Yang, S.-H., Huang, T. S., Lan, H., Teng, H., Yang, C.-Y., Tsai, Y., Lin, C.-H., Wang, H., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb2910 · Cited by 303 · see citing works
A two-step model for colon adenoma initiation and progression caused by APC loss
Phelps, R. A., Chidester, S., Dehghanizadeh, S., Phelps, J., Sandoval, I. T., Rai, K., Broadbent, T., Sarkar, S., Burt, R. W., & Jones, D. A. (2009) · Cell · doi:10.1016/j.cell.2009.02.037 · Cited by 286 · see citing works
Shakoori, A., Ougolkov, A. V., Yu, Z. W., Zhang, B., Modarressi, M. H., Billadeau, D. D., Mai, M., Takahashi, Y., & Minamoto, T. (2005) · PubMed · doi:10.1016/j.bbrc.2005.07.041 · Cited by 272 · see citing works
ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer
Cai, C., Wang, H., He, H. H., Chen, S., He, L., Ma, F., Mucci, L. A., Wang, Q., Fiore, C., Sowalsky, A. G., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66666 · Cited by 271 · see citing works
Self-citationQi, J., Yu, Y., Öztürk, Ö. A., Holland, J. D., Besser, D., Fritzmann, J., Wulf-Goldenberg, A., Eckert, K., Fichtner, I., & Birchmeier, W. (2015) · Gut · doi:10.1136/gutjnl-2014-307900 · Cited by 179 · see citing works
APC Is Essential for Targeting Phosphorylated β-Catenin to the SCFβ-TrCP Ubiquitin Ligase
Su, Y., Fu, C., Ishikawa, S., Stella, A., Kojima, M., Shitoh, K., Schreiber, E. M., Day, B. W., & Liu, B. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.023 · Cited by 174 · see citing works
Fang, Z., Tang, J. P., Bai, Y., Lin, H., You, H., Jin, H., Lin, L., You, P., Li, J., Zhang, D., et al. (2015) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-015-0198-6 · Cited by 156 · see citing works
HOXB7 as a Prognostic Factor and Mediator of Colorectal Cancer Progression
Liao, W., Jiang, D., Yuan, J., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2533 · Cited by 154 · see citing works
Self-citationChung, M.-T., Lai, H., Sytwu, H., Yan, M., Shih, Y., Chang, C., Yu, M., Liu, H.-S., Chu, D.-W., & Lin, Y. (2008) · Gynecologic Oncology · doi:10.1016/j.ygyno.2008.10.026 · Cited by 150 · see citing works
Early detection of colorectal cancer: from conventional methods to novel biomarkers
Vatandoost, N., Ghanbari, J., Mojaver, M., Avan, A., Ghayour‐Mobarhan, M., Nedaeinia, R., & Salehi, R. (2015) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-015-1928-z · Cited by 144 · see citing works
Zhou, A.-D., Diao, L.-T., Xu, H. M., Xiao, Z.-D., Li, J.-H., Zhou, H., & Qu, L.-H. (2011) · Oncogene · doi:10.1038/onc.2011.461 · Cited by 140 · see citing works
Self-citationLiao, W., Ye, Y., Zhang, N., Li, T., Wang, S., Cui, Y., Qi, L., Wu, P., Jiao, H., Xie, Y., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4309 · Cited by 139 · see citing works
Self-citationThe clinical and biological significance of MIR-224 expression in colorectal cancer metastasis
Ling, H. Y., Pickard, K. M., Ivan, C., Isella, C., Ikuo, M., Mitter, R., Spizzo, R., Bullock, M. D., Braicu, C., Pileczki, V., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309372 · Cited by 130 · see citing works
Qi, L., Sun, B., Liu, Z., Cheng, R.-F., Li, Y., & Zhao, X. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-014-0107-4 · Cited by 128 · see citing works
Tian, X., Hou, W., Fang, Y., Fan, J., Tong, H., Bai, S., Qu, C., Xu, H. J., & Li, Y. (2013) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-32-100 · Cited by 125 · see citing works
Ji, S., Ye, G., Zhang, J., Wang, L., Wang, T., Wang, Z., Zhang, T., Wang, G., Guo, Z., Luo, Y., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-301083 · Cited by 118 · see citing works
Self-citationLiao, W., Li, T., Wang, Z.-G., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0244 · Cited by 117 · see citing works
Self-citationMicroRNA‐224 is up‐regulated in hepatocellular carcinoma through epigenetic mechanisms
Wang, Y., Toh, H. C., Chow, P. K. H., et al. (2012) · The FASEB Journal · doi:10.1096/fj.11-201855 · Cited by 114 · see citing works
Pronobis, M. I., Rusan, N. M., & Peifer, M. A. (2015) · eLife · doi:10.7554/elife.08022 · Cited by 112 · see citing works
Huang, L., Dai, T., Lin, X., et al. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.025 · Cited by 109 · see citing works
Tang, Y., Simoneau, A. R., Liao, W.-X., Guo, Y., Hope, C., Liu, F., Li, S., Xie, J., Holcombe, R. F., JURNAK, F. A., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0885 · Cited by 101 · see citing works
Self-citationLu, Y., Li, Y., Xue, X., Zhou, M., Liu, Y., Zhang, C., Li, J., Zheng, L., Hong, M., & Li, X. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2348 · Cited by 94 · see citing works
Tang, D., Liu, J., Wang, D., et al. (2011) · Clinical and investigative medicine · doi:10.25011/cim.v34i1.15105 · Cited by 91 · see citing works
Grassilli, E., Narloch, R., Federzoni, E. A., Ianzano, L., Pisano, F., Giovannoni, R., Romano, G., Masiero, L., Leone, B. E., Bonin, S., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3289 · Cited by 91 · see citing works
Coordinated Action of CK1 Isoforms in Canonical Wnt Signaling
del Valle‐Pérez, B., Arqués, O., Vinyoles, M., de Herreros, A. G., & Duñach, M. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01466-10 · Cited by 83 · see citing works
Yamada, N. O., Noguchi, S., Mori, T., Naoe, T., Maruo, K., & Akao, Y. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.02.060 · Cited by 80 · see citing works
MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer
Zhang, W., Zhang, T., Jin, R., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-014-0113-6 · Cited by 80 · see citing works
Failor, K. L., Desyatnikov, Y., Finger, L. A., & Firestone, G. L. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0143 · Cited by 76 · see citing works
MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly targeting DLC1
Zhang, G., Li, J., Zhou, H., Xiao, H.-X., Li, Y., & Zhou, T. (2015) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-015-0189-7 · Cited by 73 · see citing works
Reed, K. R., Athineos, D., Méniel, V. S., Wilkins, J. A., Ridgway, R. A., Burke, Z. D., Muncan, V., Clarke, A. R., & Sansom, O. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805778105 · Cited by 69 · see citing works
Gopal, U., Jayanthi, V., Devaraj, N., & Devaraj, H. (2007) · Molecular Carcinogenesis · doi:10.1002/mc.20311 · Cited by 68 · see citing works
Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway
Lu, F., Sun, Y., Wei, C. Y., et al. (2014) · Nature Communications · doi:10.1038/ncomms6368 · Cited by 59 · see citing works
Reduction of miR-29c enhances pancreatic cancer cell migration and stem cell-like phenotype
Jiang, J., Yu, C., Chen, M., Zhang, H., Tian, S., & Sun, C. (2014) · Oncotarget · doi:10.18632/oncotarget.3089 · Cited by 46 · see citing works
MicroRNAs - A New Generation Molecular Targets for Treating Cellular Diseases
Paulmurugan, R. (2013) · Theranostics · doi:10.7150/thno.8113 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Chiarelli, N., Ritelli, M., Zoppi, N., & Colombi, M. (2019) · Genes · doi:10.3390/genes10080609 · Cited by 82 · see citing works
- Authors
- Li, T., Lai, Q., Wang, S., Cai, J., Xiao, Z., Deng, D., He, L., Jiao, H., Ye, Y., Liang, L., Ding, Y., & Liao, W.
- Affiliations
- Nanfang Hospital (CN)
- Corresponding author
- Liao, Wenting
- ORCID
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2016-01-29
- Volume
- 35
- Issue
- 1
- Pages
- 21-21
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- PMC
- PMC4731927
- OpenAlex
- W2274179863
- Cited by
- 92
- References
- 50
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 6 · 2022: 16 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 13 · 2016: 7
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-04-27)
- Open access
- gold
- doi.org
- Locations
- Journal of Experimental & Clinical Cancer Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Basic Research Program of China (2015CB554002, 2010CB529403)
- National Natural Science Foundation of China (NSFC)-Guangdong Joint Fund (U1201226)
- Major Projects of the National Natural Science Foundation of China (81090422)
- National Natural Science Foundation of China (81172055, 81472313, 81472710)
- National Science Foundation for Young Scientists of China (81402375)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-224, Wnt/β-catenin signaling, colorectal cancer, GSK3β, SFRP2, β-catenin nuclear translocation, metastasis, cell proliferation, microRNA target regulation, 3' untranslated region
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Secreted Frizzled-Related Proteins, Animals, Cell Movement, Humans, Membrane Proteins, Neoplasm Metastasis, Neoplasm Transplantation, Colorectal Neoplasms, 3' Untranslated Regions, MicroRNAs, Glycogen Synthase Kinase 3, HCT116 Cells, Cell Line, Tumor, Cell Proliferation, Mice, Wnt Signaling Pathway
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
