MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells
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Abstract
MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for either cleavage or repression of translation. The roles of miRNAs in lineage determination and proliferation as well as the location of several miRNA genes at sites of translocation breakpoints or deletions has led to the speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state. Here we show that the highly malignant human brain tumor, glioblastoma, strongly overexpresses a specific miRNA, miR-21. Our studies show markedly elevated miR-21 levels in human glioblastoma tumor tissues, early-passage glioblastoma cultures, and in six established glioblastoma cell lines (A172, U87, U373, LN229, LN428, and LN308) compared with nonneoplastic fetal and adult brain tissues and compared with cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes.
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miR-21 is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins.
“Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins.”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [5]
miR-21 expression is upregulated in GBMs.
“We have previously demonstrated that miR-21 expression is upregulated in GBMs (5).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [5]
miR-21 expression is highly upregulated in a variety of solid tumors, including GBM, breast, lung, colon, prostate, pancreas, and stomach cancers.
“Its expression is highly upregulated in a variety of solid tumors, including GBM, breast, lung, colon, prostate, pancreas, and stomach cancers (5, 54).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [5]
The 2'-O-MOE miR-21 ASO induced many proapoptotic and cell cycle arrest genes but did not significantly and consistently change the viability of glioma cell lines.
“We note that, though 2′-O-MOE miR-21 ASO induced many proapoptotic and cell cycle arrest genes (Fig. 2C; also see Table S1 in the supplemental material), it did not significantly and consistently change the viability of glioma cell lines, which was reported for other, less potent miR-21 inhibitors (5, 8).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [5]
Elevated miR-21 expression has been causally linked to proliferation, apoptosis, and migration of several cancer cell lines.
“Elevated miR-21 expression has been causally linked to proliferation, apoptosis, and migration of several cancer cell lines (1, 5, 44, 60).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [5]
miR-21 has been shown to be a strong antiapoptotic factor.
“In particular, miRNA-21 (miR-21) has been shown to be a strong antiapoptotic factor [5, 9–11].”
From MicroRNA‐21 protects neurons from ischemic death (2010) · cites this paper as [5]
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 [5]
Knockdown of miR-21 in cultured glioblastoma cells activates caspases leading to apoptotic cell death, suggesting miR-21 is an anti-apoptotic factor.
“Knockdown of miR-21 in cultured glioblastoma cells activates caspases leading to apoptotic cell death, suggesting miR-21 is an anti-apoptotic factor (Chan et al., 2005).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Chan et al., 2005
miR-21 expression is increased in glioblastoma, head and neck carcinomas, ovarian cancer, B-cell lymphoma, hepatocellular, and cervical carcinoma.
“Further miRNA profiling in tumor samples and cancer cell lines show increased miR-21 expression in glioblastoma (Chan et al., 2005; Ciafre et al., 2005), head and neck carcinomas (Tran et al., 2007), ovarian cancer (Iorio et al., 2007), B-cell lymphoma (Lawrie et al., 2007), hepatocellular (Meng et al., 2007), and cervical carcinoma (Lui et al., 2007).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Chan et al., 2005
Knock-down of miR-21 in glioblastoma cell lines triggers the activation of caspases and increases apoptosis.
“Knock-down of miR-21 in glioblastoma cell lines triggers the activation of caspases and increases apoptosis (Chan et al., 2005).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Chan et al., 2005
miR-21 is up-regulated in the majority of human cancers profiled to date.
“The majority of these profiling studies have reported increased levels of miR-21 in most human cancers (6,(8)(9)(10).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [6]
Inhibition of miR-21 by LNA or 2'-O-Me-miR-21 led to increased caspase-dependent apoptosis in glioblastoma cells, suggesting miR-21 acts as an oncogene to inhibit apoptosis.
“In the same study, inhibition of miR-21 by LNA or 2 ¶O-Me-miR-21 led to increased caspase-dependent apoptosis, suggesting that miR-21 could be acting as an oncogene to inhibit apoptosis in glioblastoma cells (6).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [6]
High levels of miR-21 were first reported in glioblastoma tumors and cell lines.
“High levels of miR-21 were first reported in glioblastoma tumors and cell lines (6).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [6]
miR-21 knockdown significantly increased apoptotic cells.
“When miR-21 levels were decreased, we observed a significant increase in apoptotic cells, as has been previously reported (6).”
From MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells (2008) · cites this paper as [6]
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- Authors
- Chan, J. A., Krichevsky, A. M., & Kosik, K. S.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- University of California, Santa Barbara (US)
- Venue
- Cancer Research
- Published
- 2005-07-15
- Volume
- 65
- Issue
- 14
- Pages
- 6029-6033
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2104610341
- Cited by
- 2,557
- References
- 3
- Citations by year
- 2026: 28 · 2025: 29 · 2024: 39 · 2023: 51 · 2022: 62 · 2021: 87 · 2020: 98 · 2019: 100 · 2018: 100 · 2017: 111 · 2016: 135 · 2015: 178 · 2014: 157 · 2013: 195 · 2012: 222
- FWCI
- 43.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS46569, R21NS046569)
- 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 › Genetics › Glioma Diagnosis and Treatment
- Keywords
- miR-21, glioblastoma, apoptosis, anti-apoptotic factors, caspase activation, microRNA overexpression, glioblastoma cell lines, microRNA knockdown
- MeSH terms
- Brain Neoplasms, Glioblastoma, Humans, Oligonucleotides, Transfection, Apoptosis, MicroRNAs, Cell Line, Tumor
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