Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 513, Issue 2, Pages 340-346Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.03.155
Keywords
Histone methyltransferase; High-grade serous ovarian carcinoma; SMYD2; Poly ADP ribose polymerase inhibitor; Non-histone methylation; LLY-507; Apoptosis
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18K09249, 15K10705, 17K11268, 187100000488, 16K21330]
- Grants-in-Aid for Scientific Research [17K11268, 18K09249, 15K10705] Funding Source: KAKEN
Ask authors/readers for more resources
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. (C) 2019 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available