AI Article Synopsis
- Dysfunction of histone methylation, particularly involving the enzyme SMYD2, is linked to cancer progression, and this study focuses on its role in high-grade serous ovarian carcinomas (HGSOCs).
- Researchers found that SMYD2 is significantly overexpressed in HGSOC tissues and demonstrated that inhibiting SMYD2 led to reduced cell growth and increased apoptosis in HGSOC cells.
- Additionally, the selective SMYD2 inhibitor LLY-507 showed potential as a standalone treatment and in combination with the PARP inhibitor olaparib, indicating a promising therapeutic strategy for patients with HGSOC.
Article Abstract
Dysfunction of histone methylation is known to be related to cancer progression. The histone methyltransferase SMYD2 methylates histone protein H3 and non-histone proteins, including poly ADP ribose polymerase 1 (PARP1). There have been reports of SMYD2 overexpression in several types of cancers. However, there are no reports regarding its role in high-grade serous ovarian carcinomas (HGSOCs). Therefore, we investigated the expression profile and conducted functional analysis on SMYD2 in HGSOC cells. In addition, we verified whether SMYD2 inhibition increases the susceptibility of HGSOC cells to PARP inhibitors. We analyzed the expression of histone methyltransferase SMYD2 by quantitative real-time polymerase chain reaction and immunohistochemistry using HGSOC clinical tissues (n = 35). We performed functional analyses, including cell proliferation assay, cell cycle analysis, and immunoblotting, after treatment with SMYD2 siRNAs and SMYD2 selective inhibitor LLY-507 in HGSOC cells. We also performed colony-formation assay after combination treatment with LLY-507 and PARP inhibitor olaparib in HGSOC cells. The expression profiles of SMYD2 showed significant overexpression of SMYD2 in HGSOC clinical tissues. The knockdown or inhibition of SMYD2 by siRNAs or LLY-507, respectively, suppressed cell growth by increasing the proportion of apoptotic cells. LLY-507 showed additive effect with olaparib in the colony-formation assay. These findings suggest that LLY-507 can be used alone or in combination with a PARP inhibitor for the treatment of patients with HGSOC.
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| http://dx.doi.org/10.1016/j.bbrc.2019.03.155 | DOI Listing |
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