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SET and MYND domain-containing protein 3 inhibits tumor cell sensitivity to cisplatin
Lei Wang1,2, Man-Li Xu1,2, Chang Wang1,2
1Key Laboratory of Industrial Fermentation Microbiology, Tianjin University of Science and Technology, Ministry of Education, Tianjin 300457, P.R. China.
Abstract:
Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3'-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation.
Insights
SET and MYND domain-containing protein 3 (SMYD3) impacts tumor sensitivity to cisplatin chemotherapy. Reducing SMYD3 enhances cisplatin effectiveness, suggesting SMYD3 as a target for overcoming cisplatin resistance in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cisplatin resistance is a significant challenge in cancer chemotherapy.
- SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase, is implicated in tumor development.
Purpose of the Study:
- To investigate the role of SMYD3 in cisplatin resistance in breast cancer cells.
- To determine if SMYD3 affects tumor cell sensitivity to cisplatin chemotherapy.
Main Methods:
- Real-time quantitative PCR (qPCR) and Western blotting to assess SMYD3 expression.
- Luciferase reporter assays to evaluate transcriptional activity.
- MTT and clonogenic assays to measure cell viability and proliferation.
- Small interfering RNA (siRNA) for SMYD3 knockdown and plasmid transfection for overexpression.
Main Results:
- SMYD3 showed differential expression in MCF-7 and T47D breast cancer cells, correlating with cisplatin resistance.
- SMYD3 knockdown increased cisplatin sensitivity and enhanced cisplatin-induced apoptosis.
- SMYD3 overexpression decreased cisplatin sensitivity.
- SMYD3 expression and its 3'-untranslated region's transcriptional activity were downregulated during cisplatin treatment.
Conclusions:
- SMYD3 plays a role in regulating sensitivity to cisplatin chemotherapy.
- SMYD3 contributes to the development of cisplatin resistance.
- MicroRNA-124 may be involved in SMYD3-mediated regulation of cisplatin resistance.
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