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Integrated transcriptomic and proteomic analysis reveals the mechanistic role of OST in cutaneous squamous cell
Yue Wang1, Hongfang Ding2, Tong Gao1
1Department of Dermatology, The Affiliated Hospital of Guilin Medical University, Guilin, China.
Abstract:
Osthole (OST) is a natural component of the traditional Chinese medicinal herb, Cnidium monnieri, that exhibits antipruritic properties and may exert effects on dermatitis. Numerous previous studies have focused on the effects of OST in tumors; however, the potential impact on cutaneous squamous cell carcinoma (CSCC) remains to be fully elucidated. Thus, the present study aimed to evaluate CSCC cell proliferation following treatment with OST, and further analyzed the underlying mechanisms using multi-omics analyses. Due to their cancerous characteristics, both A431 and SCL-1 cells are used in drug screening and testing for CSCC, particularly for therapies targeting growth pathways and markers associated with SCC. Results of the flow cytometry analysis demonstrated that OST impacted the CSCC cell cycle, causing arrest in the G2 phase. Notably, OST exerted a slight growth-promoting effect on healthy skin HaCaT cells. In addition, our omics results revealed that there were 1,720 differentially expressed genes and 227 differentially expressed proteins in the OST-treated group. Transcriptomics combined with proteomics analyses revealed that 5 of the top 20 screened pathways were associated with the cell cycle, and ATR, CENPJ, and RAD54B were highlighted as specific targets for OST-mediated regulation. Collectively, these results suggested that OST has a potential inhibition on human CSCC cells, and ATR, CENPJ, and RAD54B may be the key factors regulated by OST in A431's cell cycle progression inhibition.
Insights
Osthole (OST) may inhibit cutaneous squamous cell carcinoma (CSCC) by arresting the cell cycle. This natural compound, derived from Cnidium monnieri, shows potential as an anti-CSCC therapy by regulating key genes and proteins.
Area of Science:
- Dermatology
- Oncology
- Pharmacology
Background:
- Osthole (OST), a natural compound from Cnidium monnieri, has known antipruritic effects and potential in dermatitis.
- Previous research on OST primarily focused on its effects in various tumors.
- The specific impact of OST on cutaneous squamous cell carcinoma (CSCC) requires further investigation.
Purpose of the Study:
- To evaluate the effect of OST on CSCC cell proliferation.
- To elucidate the underlying molecular mechanisms of OST's action in CSCC using multi-omics analyses.
- To identify potential therapeutic targets for CSCC treated with OST.
Main Methods:
- Utilized A431 and SCL-1 cell lines for CSCC drug screening.
- Performed flow cytometry to analyze the cell cycle.
- Conducted multi-omics analyses (transcriptomics and proteomics) to identify differentially expressed genes and proteins.
Main Results:
- OST induced G2 phase arrest in CSCC cells.
- A slight growth-promoting effect of OST was observed in healthy HaCaT cells.
- Identified 1,720 differentially expressed genes and 227 differentially expressed proteins upon OST treatment.
- Multi-omics data highlighted cell cycle-associated pathways and specific targets: ATR, CENPJ, and RAD54B.
Conclusions:
- OST demonstrates potential inhibitory effects on human CSCC cells.
- ATR, CENPJ, and RAD54B are identified as key factors potentially regulated by OST in inhibiting CSCC cell cycle progression.
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