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Published on: April 12, 2024
Essential genes analysis reveals small ribosomal subunit protein eS28 may be a prognostic factor and potential
Chao Liang1,2, Juan Zhou3, Yongjie Wang4
1Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China.
Background:
Osteosarcoma, the most common primary malignant bone tumor, is currently treated with surgery combined with chemotherapy, but the limited availability of targeted drugs contributes to a poor prognosis. Identifying effective therapeutic targets is crucial for improving the prognosis of osteosarcoma patients.
Methods:
We screened the DepMap database to identify essential genes as potential therapeutic targets for osteosarcoma. Gene Set Enrichment Analysis (GSEA) was employed to elucidate the biological roles of these essential genes. Promising candidates were filtered through univariate and multivariate Cox analyses, as well as Kaplan-Meier survival analyses using the GSE21257-OSA and TARGET-OSA datasets. The functional role of the target gene was assessed through cell experiments. Additionally, an in situ nude mice model was established to observe the gene's function, and RNA sequencing was utilized to explore the underlying molecular mechanism.
Results:
A total of 934 essential genes were identified based on their effects (Chronos) using the DepMap database. These genes were primarily enriched in the ribosome pathway according to GSEA analysis. Among them, 195 genes were associated with the ribosome pathway. Rps28, Rps7, and Rps25 were validated as promising candidates following univariate and multivariate Cox analyses of the TARGET-OSA and GSE21257-OSA datasets. Kaplan-Meier survival analyses indicated Rps28 represented an especially promising target, with high expression correlating with poor prognosis. Knockdown of small ribosomal subunit protein eS28, the protein of Rps28, inhibited proliferation, migration, and invasion in both in vitro and in vivo experiments. Silencing RPS28 affected the MAPK signaling pathway in osteosarcoma.
Conclusion:
In summary, Rps28 has been identified as an essential gene for osteosarcoma cell survival and eS28 may serve as a potential vulnerability in osteosarcoma.
Insights
Researchers identified RPS28 as a key gene in osteosarcoma. Targeting RPS28, or its protein eS28, could be a new strategy to treat this bone cancer and improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma, a primary bone malignancy, has limited targeted therapies, leading to poor patient prognosis.
- Identifying novel therapeutic targets is critical for advancing osteosarcoma treatment strategies.
Purpose of the Study:
- To screen the DepMap database for essential genes as potential therapeutic targets in osteosarcoma.
- To elucidate the biological roles of essential genes and validate promising candidates for osteosarcoma treatment.
Main Methods:
- Screened DepMap database for essential genes; utilized Gene Set Enrichment Analysis (GSEA) for pathway enrichment.
- Performed univariate/multivariate Cox and Kaplan-Meier survival analyses on TARGET-OSA and GSE21257-OSA datasets.
- Conducted in vitro/in vivo experiments and RNA sequencing to assess gene function and molecular mechanisms.
Main Results:
- Identified 934 essential genes, with significant enrichment in the ribosome pathway (195 genes).
- RPS28, RPS7, and RPS25 emerged as promising candidates; RPS28 showed high expression linked to poor prognosis.
- RPS28 knockdown inhibited osteosarcoma cell proliferation, migration, and invasion, affecting the MAPK signaling pathway.
Conclusions:
- RPS28 is identified as an essential gene for osteosarcoma cell survival.
- The protein eS28, encoded by RPS28, represents a potential therapeutic vulnerability for osteosarcoma.
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