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A DNA Aptamer as a Chemical Tool to Modulate MEX3C-Mediated mRNA Destabilization
Tongqing Li1,2, Jingjing Qin1,2, Zihao Huang2,3
1College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310000, China.
ACS Applied Bio Materials
|January 10, 2026
Summary
Researchers developed a DNA aptamer, MRiApt-PT-stem, to target the RNA-binding protein MEX3C. This probe effectively modulates gene expression, restores tumor antigen presentation, and offers a new strategy for targeting undruggable cancer genes.
Area of Science:
- Molecular Biology
- Cancer Research
- Drug Discovery
Background:
- RNA-binding proteins (RBPs) control gene expression via mRNA turnover.
- MEX3C is a tumor-specific RBP that destabilizes transcripts.
- Selective tools to target MEX3C are currently unavailable.
Purpose of the Study:
- To develop a high-affinity DNA aptamer targeting MEX3C.
- To create a chemical probe for modulating MEX3C activity.
- To investigate MEX3C's role in cancer prognosis.
Main Methods:
- Iterative Blocker-SELEX selection and sequence optimization.
- Characterization of aptamer binding affinity and specificity.
- Assessment of aptamer efficacy in cell-based assays and TCGA data analysis.
Main Results:
- A high-affinity DNA aptamer, MRiApt, targeting MEX3C's KH1 domain was developed.
- A stabilized derivative, MRiApt-PT-stem, showed enhanced stability and cellular uptake.
- MRiApt-PT-stem antagonized MEX3C, restored HLA-A2 expression, and improved T cell recognition.
- High MEX3C expression correlated with poor prognosis in liver hepatocellular carcinoma.
Conclusions:
- MRiApt-PT-stem serves as a valuable chemical probe for studying MEX3C.
- This aptamer enables modulation of MEX3C-mediated post-transcriptional regulation.
- The findings support targeting RBPs like MEX3C for cancer therapy and transcriptome modulation.
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