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Published on: March 18, 2014
TRIM58 Interacts with Pyruvate Kinase M2 to Inhibit Tumorigenicity in Human Osteosarcoma Cells
Peng Yuan1, Yiyi Zhou1, Rui Wang1
1Department of Orthopaedics, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214000, China.
Background:
Tripartite motif containing 58 (TRIM58), an E3 ubiquitin ligase, is reported as a suppressor gene in certain human tumors. However, the biological function of TRIM58 in osteosarcoma (OS) is still less identified.
Methods:
In the present study, TRIM58 induced silencing and overexpression in OS cells using RNA interference (RNAi) and lentiviral-mediated vector, respectively. Cell proliferation profiles were analyzed using cell counting kit-8 (CCK-8) assay. Cell apoptosis profiles were determined using a flow cytometer. qRT-PCR and western blot were used to determine gene expression. Coimmunoprecipitation (Co-IP) assay was used to examine protein interaction.
Results:
Our results demonstrated TRIM58 was downregulated in human OS tissues. Overexpression of TRIM58 remarkably suppressed the growth of OS cells and decreased glucose transportation and lactate secretion. These results indicated that TRIM58 involved in the regulation of energy metabolism in OS cells. Importantly, TRIM58 interacted with pyruvate kinase M2 (PKM2) in OS cells. Moreover, TRIM58 might inhibit the activity of PKM2 through enhancing its polyubiquitination in OS cells.
Conclusions:
This analysis not only explored a deep understanding of the biological function of TRIM58 but also indicated its signaling pathway in OS cells.
Insights
Tripartite motif containing 58 (TRIM58) acts as a tumor suppressor in osteosarcoma (OS). TRIM58 inhibits OS cell growth and regulates energy metabolism by interacting with pyruvate kinase M2 (PKM2).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tripartite motif containing 58 (TRIM58) functions as an E3 ubiquitin ligase and is recognized as a tumor suppressor gene in various human cancers.
- The specific biological role of TRIM58 in osteosarcoma (OS) remains largely uncharacterized.
Purpose of the Study:
- To elucidate the function of TRIM58 in osteosarcoma (OS).
- To investigate the underlying molecular mechanisms and signaling pathways of TRIM58 in OS.
Main Methods:
- TRIM58 expression was manipulated in OS cells using RNA interference (RNAi) for silencing and lentiviral vectors for overexpression.
- Cell proliferation was assessed using the cell counting kit-8 (CCK-8) assay, and apoptosis was analyzed via flow cytometry.
- Gene expression levels were quantified using qRT-PCR and Western blot, while protein interactions were examined using co-immunoprecipitation (Co-IP) assays.
Main Results:
- TRIM58 was found to be downregulated in human OS tissues.
- Overexpression of TRIM58 significantly inhibited OS cell proliferation, glucose uptake, and lactate production, indicating its role in regulating energy metabolism.
- TRIM58 was observed to interact with pyruvate kinase M2 (PKM2) in OS cells, potentially inhibiting PKM2 activity through enhanced polyubiquitination.
Conclusions:
- This study reveals the tumor-suppressive function of TRIM58 in osteosarcoma.
- The findings highlight TRIM58's involvement in regulating energy metabolism and its interaction with PKM2, offering insights into its signaling pathway in OS.
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