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Updated: Jun 14, 2026
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Published on: August 25, 2021
CPSF2-mediated 3' UTR truncation of MTERF3 drives mitochondrial dysfunction and osteosarcoma progression
Ying Zhang1, Weiqing Lu2, Zikun Huang3
1Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China. 47122404@qq.com.
Oncogene
|June 12, 2026
Summary
Alternative polyadenylation (APA) shortens MTERF3 3' UTRs in osteosarcoma, promoting tumor growth. This shortening, driven by CPSF2, leads to increased MTERF3 protein and disrupts tumor suppressor gene expression, indicating poor prognosis.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Alternative polyadenylation (APA) is a key post-transcriptional regulator implicated in cancer.
- The precise role of APA in osteosarcoma (OS) tumorigenesis is not fully understood.
Purpose of the Study:
- To investigate the role and mechanisms of APA in osteosarcoma progression.
- To identify APA events linked to OS patient prognosis and gene expression.
Main Methods:
- Analysis of APA events in osteosarcoma tissues.
- Correlation analysis to identify upstream regulators.
- Functional assays in OS cells to assess the impact of 3' UTR length.
Main Results:
- Recurrent shortening of MTERF3 3' UTRs in OS tumors correlated with poor prognosis and increased MTERF3 mRNA.
- Shorter MTERF3 3' UTRs enhanced OS cell proliferation, migration, and invasion.
- CPSF2 was identified as an upstream regulator promoting MTERF3 3' UTR shortening via proximal polyadenylation site usage, leading to MTERF3 protein upregulation and loss of miR-182-5p binding.
- Shortened MTERF3 3' UTR disrupted ceRNA crosstalk, downregulating the tumor suppressor ADCY6.
Conclusions:
- CPSF2-mediated APA of MTERF3 3' UTR shortening promotes osteosarcoma progression.
- This mechanism involves increased MTERF3 protein levels and disruption of tumor suppressor pathways.
- APA represents a potential therapeutic target in osteosarcoma.
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