Depletion of H3K79 methyltransferase Dot1L promotes cell invasion and cancer stem-like cell property in ovarian cancer.
Depletion of H3K79 methyltransferase Dot1L promotes cell invasion and cancer stem-like cell property in ovarian cancer.
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H3K79 甲基转移酶 Dot1L 的耗竭可促进卵巢癌中的细胞侵袭和癌症干细胞样细胞特性。
DOI：
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发表时间：
2019-02
影响因子：
2.2
通讯作者：
Qiang Wu
中科院分区：
文献类型：
--
作者：
Xian Wang;Hua Wang;Bo Xu;Dongrui Jiang;Shan Huang;Hongzhen Yu;Zhengsheng Wu;Qiang Wu
DOT1样蛋白(DOT1L)是组蛋白H3中赖氨酸79甲基化的唯一甲基转移酶。依赖于DOT1L的H3K79甲基化参与了许多生物学过程，包括端粒沉默、细胞周期调节、转录激活和DNA修复。全基因组测序研究发现，DOT1L基因在包括卵巢癌在内的多种人类恶性肿瘤中反复发生缺失和突变，但DOT1L在卵巢癌中的作用尚不清楚。为了证实DOT1L在卵巢癌中的作用，本研究利用CRISPR/Cas9技术对DOT1L在卵巢癌细胞中的表达进行了敲除。DOT1L缺失对卵巢癌细胞的生长影响较小，但可显著促进卵巢癌细胞的侵袭，并诱导卵巢癌细胞具有肿瘤干细胞样特性。机制上，DOT1L的缺失下调了紧密连接标志物E-钙粘附素和TJP1的表达，并通过Wnt信号激活上调了ALDH1A1的表达。我们的数据表明DOT1L在卵巢癌中具有潜在的肿瘤抑制作用，这与卵巢癌患者中观察到的DOT1L基因的缺失有关，进一步的研究将进一步阐明DOT1L在卵巢癌发生发展中的作用。
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.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
5.5
作者：
Wood K;Tellier M;Murphy S
通讯作者：
Murphy S
DOI：
10.1158/1541-7786.mcr-10-0398
发表时间：
2010-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Li H;Cai Q;Godwin AK;Zhang R
通讯作者：
Zhang R
影响因子：
2.2
作者：
Hongxing Zhao;Wengen Hou;Jingang Tao;Yilei Zhao;G. Wan;Chao Ma;Haibin Xu
通讯作者：
Hongxing Zhao;Wengen Hou;Jingang Tao;Yilei Zhao;G. Wan;Chao Ma;Haibin Xu
EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
影响因子：
8
作者：
Singh, A.;Settleman, J.
通讯作者：
Settleman, J.