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Updated: Dec 23, 2025
A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
Published on: June 16, 2022
microRNA-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant cell proliferation in human
Jian Lu1, Hongming Ji2, Huoquan Tang1
1Department of Neurosurgery, General Hospital of TISCO, Shanxi Medical University, Taiyuan, China.
Abstract:
Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. Recent research has revealed the key role of aberrant EZH2 hyper-activity in human gliomas. Here, we examined the role of the lesser-known PRC2-associated PHD Finger Protein 19 (PHF19) in human glioma. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. miR-124a over-expression in the A172 and U251MG glioma cell lines and patient glioma cells suppressed PHF19 expression, EZH2 activation, and cell proliferation. However, miR-124a did not suppress cell proliferation with PHF19 silencing or mutation. Knockdown of PHF19 suppressed EZH2 phosphorylation and proliferation of glioma cells. Co-immunoprecipitation confirmed that PHF19 forms the PRC2 with EZH2, EED, and SUZ12. In a nude murine model, subcutaneous and orthotopic xenograft tumor growth was significantly inhibited by miRNA-124a or PHF19 shRNA. In conclusion, miR-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant glioma cell proliferation. Targeting PHF19 via miR-124a agomir therapy may block aberrant EZH2 hyper-activity in these tumors.
Insights
MicroRNA-124a suppresses glioma cell proliferation by inhibiting PHF19 and EZH2 activation. Targeting PHF19 with miR-124a therapy may offer a new treatment strategy for gliomas.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Enhancer of Zeste 2 (EZH2) is crucial in Polycomb Repressive Complex 2 (PRC2) and implicated in oncogenesis.
- Aberrant EZH2 hyperactivity is a key factor in human gliomas.
Purpose of the Study:
- To investigate the role of PHD Finger Protein 19 (PHF19), a PRC2-associated protein, in human glioma.
- To explore the therapeutic potential of targeting PHF19 and EZH2 in glioma.
Main Methods:
- Quantified PHF19 and miR-124a levels in glioma tissues and cell lines.
- Utilized miR-124a overexpression, PHF19 knockdown, and co-immunoprecipitation assays.
- Assessed proliferation and EZH2 activation in vitro.
- Evaluated tumor growth inhibition in a nude murine xenograft model.
Main Results:
- PHF19 transcript and protein levels were elevated in human gliomas, inversely correlated with miR-124a.
- miR-124a overexpression suppressed PHF19, EZH2 activation, and glioma cell proliferation.
- PHF19 knockdown inhibited EZH2 phosphorylation and glioma cell proliferation.
- In vivo studies showed significant tumor growth inhibition with miR-124a or PHF19 shRNA.
Conclusions:
- miR-124a suppresses glioma cell proliferation by inhibiting PHF19 overexpression and EZH2 hyper-activation.
- PHF19 is a key component of PRC2 and plays a critical role in glioma progression.
- Targeting PHF19 with miR-124a agomir therapy presents a potential therapeutic strategy for gliomas by blocking aberrant EZH2 activity.
