MiR-125b acts as an oncogene in glioblastoma cells and inhibits cell apoptosis through p53 and p38MAPK-independent pathways
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BACKGROUND: We have recently identified miR-125b upregulation in glioblastoma (GMB). The aim of this study is to determine the correlation between miR-125b expression and malignant grades of glioma and the genes targeted by miR-125b. METHODS: Real-time PCR was employed to measure the expression level of miR-125b. Cell viability was evaluated by cell growth and colony formation in soft-agar assays. Cell apoptosis was determined by Hoechst 33342 staining and AnnexinV-FITC assay. The Luciferase assay was used to confirm the actual binding sites of p38MAPK mRNA. Western blot was used to detect the gene expression level. RESULTS: The expression level of miR-125b is positively correlated with the malignant grade of glioma. Ectopic expression of miR-125b promotes the proliferation of GMB cells. Knockdown of endogenous miR-125b inhibits cell proliferation and promotes cell apoptosis. Further studies reveal that p53 is regulated by miR-125b. However, downregulation of the endogenous miR-125b also results in p53-independent apoptotic pathway leading to apoptosis in p53 mutated U251 cells and p53 knockdown U87 cells. Moreover, p38MAPK is also regulated by miR-125b and downregulation of miR-125b activates the p38MAPK-induced mitochondria apoptotic pathway. CONCLUSION: High-level expression of miR-125b is associated with poor outcomes of GMB. MiR-125b may have an oncogenic role in GMB cells by promoting cell proliferation and inhibiting apoptosis.
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P53 is regulated by miR-125b, an oncogenic miRNA that is upregulated in glioblastoma and that inhibits cell proliferation and promotes evasion of apoptosis.
“P53 is in turn regulated by miR-125b, an oncogenic miRNA that is upregulated in GBM and that inhibits cell proliferation and promotes evasion of apoptosis [52].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [52]
The Results report that miR-125b regulates p53, and the Discussion describes its upregulation in glioblastoma tissue. But the claim reverses the proliferation finding: the Results say miR-125b promotes cell proliferation, while its knockdown inhibits proliferation and promotes apoptosis. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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- Authors
- Wu, N., Lin, X., Zhao, X., Zheng, L., Xiao, L., Liu, J., Ge, L., & Cao, S.
- Affiliations
- Chinese Academy of Sciences (CN)
- Capital Medical University (CN)
- Qingdao University (CN)
- Yellow Sea Fisheries Research Institute (CN)
- Qingdao Agricultural University (CN)
- Roswell Park Comprehensive Cancer Center (US)
- Corresponding author
- Lin, X
- Cao, S
- Venue
- British Journal of Cancer
- Published
- 2013-10-29
- Volume
- 109
- Issue
- 11
- Pages
- 2853-2863
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3844918
- OpenAlex
- W2008006957
- Cited by
- 109
- References
- 39
- Citations by year
- 2025: 8 · 2024: 2 · 2023: 9 · 2022: 6 · 2021: 7 · 2020: 30 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 12 · 2015: 13 · 2014: 5
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81273550, 81072065, 41306157)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miR-125b, glioblastoma, oncogenic microRNA, apoptosis, p53, p38 MAPK, mitochondrial apoptosis, cell proliferation, tumor grade, TP53 mutation, microRNA target regulation
- MeSH terms
- Adolescent, Adult, Aged, Animals, Brain Neoplasms, Cells, Cultured, Child, Female, Glioblastoma, Humans, Male, Middle Aged, Oncogenes, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, MicroRNAs, p38 Mitogen-Activated Protein Kinases, Rats, Young Adult, HEK293 Cells
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