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Targeting TRIM26: Unveiling an Oncogene and Identification of Plant Metabolites as a Potential Therapeutics for
Sweta H Makwana1, Tannavi Sharma1, Manas K Mahapatra1
1Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India.
Abstract:
Breast cancer is the major cause of cancer-related mortality and frequent malignancies among women worldwide. The TRIM (Tripartite Motif) protein family is a broad and diverse set of proteins that contain a conserved structural motif known as the tripartite motif, which comprises of three different domains, B-box domain, Coiled-coil domain and RBR (Ring-finger, B-box, and coiled-coil) domain. TRIM proteins are involved in regulating cancer growth and metastasis. However, TRIM proteins are still unexplored in cancer cell regulation. In this study, by using a cancer database expression of all TRIM proteins was determined in breast cancer. Out of 77 TRIM genes, 16 genes were upregulated in breast cancer. Here, the upregulated TRIM26 gene's role is not yet explored in breast cancer. Indeed, TRIM26 is upregulated in 21 cancer types out of 33 cancer types. To investigate the role of TRIM26 in breast cancer, siRNA-mediated gene silencing was carried out in MCF-7 and MDA-MB 231 breast cancer cells. Reduced expression of TRIM 26 decreased cancer cell proliferation, migration and invasion with simultaneous reduction of various proliferative, cell cycle and mesenchymal markers and upregulation of epithelial markers. Further, docking studies found potential novel plant metabolites. Thus, targeting TRIM26 may provide a novel therapeutic approach for breast cancer treatment.
Insights
Tripartite Motif 26 (TRIM26) is upregulated in breast cancer and drives cancer cell proliferation and metastasis. Silencing TRIM26 inhibited these processes, suggesting it as a potential therapeutic target for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a leading cause of cancer mortality globally.
- The Tripartite Motif (TRIM) protein family regulates cancer growth and metastasis but remains underexplored in cancer cell regulation.
- TRIM26, a member of the TRIM family, is upregulated in numerous cancer types, including breast cancer.
Purpose of the Study:
- To investigate the role of TRIM26 in breast cancer progression.
- To determine if targeting TRIM26 could offer a novel therapeutic strategy.
Main Methods:
- Analysis of TRIM gene expression in a breast cancer database.
- siRNA-mediated gene silencing of TRIM26 in MCF-7 and MDA-MB 231 breast cancer cell lines.
- Assessment of cell proliferation, migration, invasion, and expression of key markers.
- In silico molecular docking studies.
Main Results:
- 16 out of 77 TRIM genes were found to be upregulated in breast cancer.
- TRIM26 expression was significantly reduced following siRNA silencing.
- Reduced TRIM26 expression led to decreased cancer cell proliferation, migration, and invasion.
- Silencing TRIM26 modulated proliferative, cell cycle, mesenchymal, and epithelial markers.
- Docking studies identified potential plant-derived therapeutic compounds.
Conclusions:
- TRIM26 plays a crucial role in promoting breast cancer cell proliferation, migration, and invasion.
- Targeting TRIM26 presents a promising therapeutic avenue for breast cancer treatment.
- Novel plant metabolites show potential for inhibiting TRIM26 activity.
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