MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.
MicroRNAs Induce Epigenetic Reprogramming and Suppress Malignant Phenotypes of Human Colon Cancer Cells.
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microRNA诱导表观遗传重编程和抑制人类结肠癌细胞的恶性表型。
DOI：
10.1371/journal.pone.0127119
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ishii H
中科院分区：
文献类型：
--
作者：
Ogawa H;Wu X;Kawamoto K;Nishida N;Konno M;Koseki J;Matsui H;Noguchi K;Gotoh N;Yamamoto T;Miyata K;Nishiyama N;Nagano H;Yamamoto H;Obika S;Kataoka K;Doki Y;Mori M;Ishii H
虽然癌症是一种遗传性疾病，但表观遗传学改变参与了其发生和发展。先前的研究表明，使用Oct 3/4，Sox 2，Klf 4和cMyc重编程结肠癌细胞可以降低癌症恶性程度。因此，癌症重编程可能是对化疗或放疗耐药的癌细胞的有用治疗。还报道了引入内源性小尺寸非编码核糖核苷酸如microRNA（miR）302 s和miR-369- 3 p或-5p导致细胞重编程的诱导。miR比转录因子的基因小，使其可能适用于临床策略。因此，我们使用miR-302 s和miR-369- 3 p或-5p重编程结肠癌细胞。这导致抑制细胞增殖和侵袭，并刺激结肠癌细胞中的间质-上皮转化表型。重要的是，核糖核苷酸的引入导致DNA去甲基化和组蛋白修饰事件的表观遗传重编程。此外，在小鼠体内施用核糖核苷酸引起癌细胞凋亡的诱导，其涉及线粒体Bcl 2蛋白家族。本研究表明，miR-302 s和miR-369 s的导入可以诱导细胞重编程，并调节人结直肠癌的恶性表型，提示适当递送功能性小分子核糖核苷酸可能为人类恶性肿瘤的治疗开辟新的途径。
Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies have shown that reprogramming of colon cancer cells using Oct3/4, Sox2, Klf4, and cMyc reduces cancer malignancy. Therefore, cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. It was also reported that the introduction of endogenous small-sized, non-coding ribonucleotides such as microRNA (miR) 302s and miR-369-3p or -5p resulted in the induction of cellular reprogramming. miRs are smaller than the genes of transcription factors, making them possibly suitable for use in clinical strategies. Therefore, we reprogrammed colon cancer cells using miR-302s and miR-369-3p or -5p. This resulted in inhibition of cell proliferation and invasion and the stimulation of the mesenchymal-to-epithelial transition phenotype in colon cancer cells. Importantly, the introduction of the ribonucleotides resulted in epigenetic reprogramming of DNA demethylation and histone modification events. Furthermore, in vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis, which involves the mitochondrial Bcl2 protein family. The present study shows that the introduction of miR-302s and miR-369s could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.
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影响因子：
11.2
作者：
Bader AG;Brown D;Winkler M
通讯作者：
Winkler M
影响因子：
4.6
作者：
Tsuno S;Wang X;Shomori K;Hasegawa J;Miura N
通讯作者：
Miura N
影响因子：
3.7
作者：
Hossain S;Yamamoto H;Chowdhury EH;Wu X;Hirose H;Haque A;Doki Y;Mori M;Akaike T
通讯作者：
Akaike T
影响因子：
4.5
作者：
Lin, Shi-Lung;Chang, Donald C.;Ying, Shao-Yao
通讯作者：
Ying, Shao-Yao
影响因子：
5.2
作者：
Hu, Shijun;Wilson, Kitchener D.;Ghosh, Zhumur;Han, Leng;Wang, Yongming;Lan, Feng;Ransohoff, Katherine J.;Burridge, Paul;Wu, Joseph C.
通讯作者：
Wu, Joseph C.