miR-21 plays a pivotal role in gastric cancer pathogenesis and progression
Open accessAbstract
Gastric cancer causes nearly one million deaths worldwide per year. Although Helicobacter pylori infection is the main risk factor, in about 80% or more of gastric cancers, the molecular pathway underlying H. pylori infection leading to the development of gastric cancers remains unclear. Recently accumulating evidence suggests that microRNAs (miRNAs) may regulate diverse biological processes and may be important in tumorigenesis. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using TaqMan quantitative real-time PCR, we confirmed that miR-21 was significantly overexpressed in human gastric cancer tissues and cell lines. Remarkably, miR-21 was also significantly overexpressed in H. pylori-infected gastric mucosa, implying that overexpression of miR-21 in gastric cancer may be due in part to H. pylori infection. More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21. Taken together, miR-21 may be important in the initiation and progression of gastric cancers as an oncomiR, likely through regulating RECK. Our findings suggest a potential regulatory pathway in which H. pylori infection upregulates expression of miR-21, which in turn downregulates RECK, and then leads to the development of gastric cancer.
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miR-21 is upregulated in most solid tumors, including breast, colorectal and glioma.
“It is upregulated in most solid tumors, including breast, colo-rectal and glioma [5, 10, 12].”
From MicroRNA‐21 protects neurons from ischemic death (2010) · cites this paper as [12]
The Abstract reports miR-21 overexpression in diverse solid tumors and specifically describes elevated expression in breast tumors and glioblastoma. It does not establish upregulation in most solid tumors, and its mention of colon cancer concerns aberrant miRNA expression generally, not miR-21 specifically. (LLM, conf=0.85)
Experimental — accuracy not yet measuredForced over-expression of miR-21 in a human gastric cancer cell line enhanced tumor proliferation and invasion.
“Zhang et al. showed in a human gastric cancer cell line that forced over-expression of miR-21 enhanced tumor proliferation and invasion”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Zhang et al., 2008
Knock-down of miR-21 in a human gastric cancer cell line resulted in a marked reduction in proliferation and increase in apoptosis.
“knock-down of miR-21 resulted in a marked reduction in proliferation and increase in apoptosis (Zhang et al., 2008).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Zhang et al., 2008
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Cites
The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited
Fidler, I. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1098 · Cited by 4,686 · see citing works
Meng, F., Henson, R., Lang, M., Wehbe, H., Maheshwari, S., Mendell, J. T., Jiang, J., Schmittgen, T. D., & Patel, T. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.02.057 · Cited by 984 · see citing works
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Research works printed but not linked: 21
- IARC. Schistosomes, liver flukes and Helicobacter pylori. IARC working group on the evaluation of carcinogenic risks to humans. IARC Monogr Eval Carcinog Risks Hum 1994;61:1-241.
- Peek Jr RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2002;2:28-37.
- Pillai RS. MicroRNA function: multiple mechanisms for a tiny RNA? RNA 2005;11:1753-1761.
- Zamore PD, Haley B. Ribo-gnome: the big world of small RNAs. Science 2005;309:1519-1524.
- Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004;101:2999-3004.
- Calin GA, Liu CG, Sevignani C, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 2004;101:11755-11760.
- Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002;99:15524-15529.
- Michael MZ, O' Connor SM, van Holst Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003;1:882-891.
- Meng F, Henson R, Wehbe-Janek H, et al. MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007;133:647-658.
- Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antia- poptotic factor in human glioblastoma cells. Cancer Res 2005;65: 6029-6033.
- Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006;103:2257-2261.
- Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005;435:834-838.
- Si ML, Zhu S, Wu H, et al. miR-21-mediated tumor growth. Oncogene 2007;26:2799-2803.
- Zhu S, Si ML, Wu H, et al. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem 2007;282:14328-14336.
- Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:15-20.
- Krek A, Grun D, Poy MN, et al. Combinatorial microRNA target predictions. Nat Genet 2005;37:495-500.
- John B, Enright AJ, Aravin A, et al. Human MicroRNA targets. PLoS Biol 2004;2:e363.
- Roldo C, Missiaglia E, Hagan JP, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 2006;24:4677-4684.
- Esquela-Kerscher A, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259-269.
- Song SY, Son HJ, Nam E, et al. Expression of reversion-inducing- cysteine-rich protein with Kazal motifs (RECK) as a prognostic indicator in gastric cancer. Eur J Cancer 2006;42:101-108.
- Oh J, Takahashi R, Kondo S, et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 2001;107:789-800. miR-21 in gastric cancer Z Zhang et al
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Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21
Hatley, M. E., Patrick, D. M., Garcia, M. R., Richardson, J. A., Bassel-Duby, R., van Rooij, E., & Olson, E. N. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.08.013 · Cited by 626 · see citing works
“Zhang et al. (2008) showed in a human gastric cancer cell line that forced overexpression of miR-21 enhanced tumor proliferation and invasion and knock- down of miR-21 resulted in a marked reduction in proliferation and increase in apoptosis.”
MicroRNA‐21 protects neurons from ischemic death
Buller, B., Liu, X., Wang, X., Zhang, R. L., Zhang, L., Hozeska‐Solgot, A., Chopp, M., & Zhang, Z. G. (2010) · The FEBS Journal · doi:10.1111/j.1742-4658.2010.07818.x · Cited by 242 · see citing works
Self-citationYu, 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
Self-citation
- Authors
- Zhang, Z., Li, Z., Gao, C., Chen, P., Chen, J., Liu, W., Xiao, S., & Lu, H.
- Affiliations
- Shanghai Jiao Tong University (CN)
- University of Chicago (US)
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 88
- Issue
- 12
- Pages
- 1358-1366
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2168750261
- Cited by
- 477
- References
- 2
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 12 · 2023: 18 · 2022: 20 · 2021: 14 · 2020: 22 · 2019: 35 · 2018: 31 · 2017: 21 · 2016: 33 · 2015: 42 · 2014: 36 · 2013: 45 · 2012: 33
- FWCI
- 11.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Chicago
- National Natural Science Foundation of China (30670940)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-21, gastric cancer, Helicobacter pylori infection, microRNA, oncogenic microRNA, RECK, tumor suppressor, cell proliferation, cell invasion, apoptosis, tumor progression, AGS cells
- MeSH terms
- Base Sequence, Humans, Stomach Neoplasms, Helicobacter pylori, Helicobacter Infections, DNA Primers, Disease Progression, MicroRNAs, Gene Knockdown Techniques
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