Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth.

Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth.
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DOI:
10.3892/mco.2013.127
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发表时间:
2013-07
影响因子:
1.2
通讯作者:
Ishii H
Ishii H
中科院分区:
其他
文献类型:
--
作者:
Kano Y;Konno M;Ohta K;Haraguchi N;Nishikawa S;Kagawa Y;Hamabe A;Hasegawa S;Ogawa H;Fukusumi T;Noguchi Y;Ozaki M;Kudo T;Sakai D;Satoh T;Ishii M;Mizohata E;Inoue T;Mori M;Doki Y;Ishii H

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尽管食管癌是高度异质性的,并且癌症干细胞的表观遗传调控的参与是高度可疑的,但调控不同亚群的表观遗传修饰分子的生物学意义仍有待确定。使用食管癌细胞,我们研究了H3K4去甲基化酶Jumonji/Arid1b (Jarid1b) (Kdm5b/ + 1/Rbp2-h1)的功能作用,这是黑色素瘤细胞持续生长所必需的表观遗传因子。JARID1B敲低导致食管癌细胞生长、成球和侵袭能力受到抑制,并与上皮标志物表达缺失有关。然而,这些对肿瘤形成的抑制作用在免疫缺陷小鼠皮下接种这些细胞后被恢复。这些结果表明,JARID1B在维持食管癌干细胞中发挥作用,并证明了研究持续抑制该表观遗传因子在食管癌中的作用的基本原理。
Although esophageal cancer is highly heterogeneous and the involvement of epigenetic regulation of cancer stem cells is highly suspected, the biological significance of epigenetically modified molecules that regulate different subpopulations remains to be firmly established. Using esophageal cancer cells, we investigated the functional roles of the H3K4 demethylase Jumonji/Arid1b (Jarid1b) (Kdm5b/Plu-1/Rbp2-h1), an epigenetic factor that is required for continuous cell growth in melanoma. JARID1B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial marker expression. However, these inhibitory effects observed on tumor formation were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that JARID1B plays a role in maintaining cancer stem cells in the esophagus and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer.