Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1.
Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1.
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DOI：
10.1038/ncomms8318
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发表时间：
2015-06-12
影响因子：
16.6
通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
--
作者：
Takahashi, Ryou-u;Miyazaki, Hiroaki;Takeshita, Fumitaka;Yamamoto, Yusuke;Minoura, Kaho;Ono, Makiko;Kodaira, Makoto;Tamura, Kenji;Mori, Masaki;Ochiya, Takahiro
肿瘤干细胞(CSCs)已在多种类型的癌症中被发现，然而，细胞获得CSC特性的机制，如耐药和肿瘤种植能力，尚不完全清楚。在这里，我们发现microRNA-27b(miR-27b)是乳腺癌细胞中产生具有CSC特性的侧群的关键调节因子，并发现抗II型糖尿病(T2D)药物二甲双胍通过miR-27b介导的对参与T2D发展的外核苷酸焦磷酸酶/磷酸二酯酶家族成员1(ENPP1)的抑制来减少该侧群。ENPP1通过上调ABCG2转运蛋白诱导侧群的产生。ENPP1还被鉴定为26S蛋白酶体的底物，其活性在CSCs中下调。总体而言，这些结果表明，T2D相关基因在肿瘤发展中起着重要作用，其表达受到严格的mRNA和蛋白质水平的控制。MicroRNAs在获得癌细胞的干细胞样特性方面发挥了作用。在这里，作者表明，microRNA-27b通过调节ENPP1蛋白，部分地调节与糖尿病发展有关的ENPP1蛋白，介导了乳腺癌干细胞侧群的产生。
Cancer stem cells (CSCs) have been identified in various types of cancer; however, the mechanisms by which cells acquire CSC properties such as drug resistance and tumour seeding ability are not fully understood. Here, we identified microRNA-27b (miR-27b) as a key regulator for the generation of a side-population in breast cancer cells that showed CSC properties, and also found that the anti-type II diabetes (T2D) drug metformin reduced this side-population via miR-27b-mediated repression of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1), which is involved in T2D development. ENPP1 induced the generation of the side-population via upregulation of the ABCG2 transporter. ENPP1 was also identified as a substrate of the 26S proteasome, the activity of which is downregulated in CSCs. Overall, these results demonstrate that a T2D-associated gene plays an important role in tumour development and that its expression is strictly controlled at the mRNA and protein levels. MicroRNAs have a role in the acquisition of stem cell-like properties of cancer cells. Here the authors show that microRNA-27b mediates generation of a side-population of breast cancer stem cells, in part by regulating the protein ENPP1, which has been previously linked to the development of diabetes.
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影响因子：
3.7
作者：
Di Paola R;Caporarello N;Marucci A;Dimatteo C;Iadicicco C;Del Guerra S;Prudente S;Sudano D;Miele C;Parrino C;Piro S;Beguinot F;Marchetti P;Trischitta V;Frittitta L
通讯作者：
Frittitta L
影响因子：
23.9
作者：
Buckley, Shannon M.;Aranda-Orgilles, Beatriz;Strikoudis, Alexandros;Apostolou, Effie;Loizou, Evangelia;Moran-Crusio, Kelly;Farnsworth, Charles L.;Koller, Antonius A.;Dasgupta, Ramanuj;Silva, Jeffrey C.;Stadtfeld, Matthias;Hochedlinger, Konrad;Chen, Emily I.;Aifantis, Iannis
通讯作者：
Aifantis, Iannis
影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES
影响因子：
82.9
作者：
Honma, Kimi;Iwao-Koizumi, Kyoko;Ochiya, Takahiro
通讯作者：
Ochiya, Takahiro
影响因子：
11.2
作者：
Chen, ZY;Wang, XS;Tseng, CC
通讯作者：
Tseng, CC