Depletion of H3K79 methyltransferase Dot1L promotes cell invasion and cancer stem-like cell property in ovarian cancer

American Journal of Translational Research

Bo Xu¹  Dongrui Jiang²  Hua Wang³  Xian Wang⁴ 

[1] Department of Gastroenterology, The Second Peoples Hospital of Hefei, Hefei 230000, Anhui, China;Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei 230001, Anhui, China;Department of Pathology, Anhui Medical University, Hefei 230032, Anhui, China;Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China

关键词: DOT1-like protein;    ovarian cancer;    cell invasion;    cancer stem cell;    Wnt signaling;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

DOT1-like protein (Dot1L) is the sole methyltransferase for methylation of lysine 79 in histone H3. Dot1L-dependent H3K79 methylation is involved in many biological processes, including telomeric silencing, cell cycle regulation, transcriptional activation and DNA repair. Genome-wide sequencing studies have revealed recurrent deletion and mutations of Dot1L gene in many types of human malignancies including ovarian cancer, however the role of Dot1L in ovarian cancer are largely unknown. To demonstrate the role of Dot1L in ovarian cancer, the expression of Dot1L was knocked out in ovarian cancer cells using CRISPR/Cas9 technology in the present study. Dot1L loss showed minimal effect on cell growth, but significantly promoted cell invasion and induced cancer stem-like cell property in ovarian cancer cells. Mechanistically, loss of Dot1L downregulated the expression of tight junction makers E-Cadherin and TJP1 and upregulated the expression of ALDH1A1 through Wnt signaling activation. Our data indicate potential tumor suppressor function of Dot1L in ovarian cancer, which is correlated with observed deletion of Dot1L gene in ovarian cancer patients, further study is granted to elucidate the function of Dot1L in tumorigenesis and progression in ovarian cancer.

【 授权许可】

CC BY-NC