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.

Oncology Letters
|April 10, 2020
PubMed

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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