MiR-101 is involved in human breast carcinogenesis by targeting Stathmin1.
MiR-101 is involved in human breast carcinogenesis by targeting Stathmin1.
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DOI：
10.1371/journal.pone.0046173
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Wang R;Wang HB;Hao CJ;Cui Y;Han XC;Hu Y;Li FF;Xia HF;Ma X
microRNA-101（miR-101）表达与几种实体上皮癌中的肿瘤生长和血管形成呈负相关。然而，miR-101在人类乳腺癌中的作用仍然难以捉摸。 MiR-101在不同亚型乳腺癌组织中的表达均较癌旁正常乳腺组织明显降低（P<0.01）。在ER α阳性和ER α阴性乳腺癌细胞及正常乳腺细胞中，miR-101的上调可抑制细胞增殖、迁移和侵袭，并促进细胞凋亡。下调miR-101对细胞生长和转移表现出相反的作用。进一步研究发现，miR-101与Stathmin 1（Stmn 1）的表达呈显著负相关，miR-101可与Stmn 1的3′-非翻译区（UTR）结合，抑制Stmn 1的翻译。过表达Stmn 1可部分恢复miR-101对细胞生长和转移的抑制作用。Stmn 1的敲低减弱了miR-101介导的细胞生长和转移增强的下调。更重要的是，体内分析发现，与miR-101下调相反，Stmn 1 mRNA和蛋白水平在不同亚型的人乳腺癌组织中均显著升高。本研究表明，人类乳腺癌组织不同亚型中miR-101的下调与靶向Stmn 1增加细胞增殖和侵袭力有关，这凸显了乳腺癌中新的调节机制，可能为未来乳腺癌的临床诊断提供有价值的线索。
MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and blood vessel formation in several solid epithelial cancers. However, the role of miR-101 in human breast cancer remains elusive. MiR-101 was significantly decreased in different subtypes of human breast cancer tissues compared with that in adjacent normal breast tissues (P<0.01). Up-regulation of miR-101 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in ER alpha-positive and ER alpha-negative breast cancer cells and normal breast cells. Down-regulation of miR-101 displayed opposite effects on cell growth and metastasis. Further investigation revealed a significant inverse correlation between the expression of miR-101 and Stathmin1 (Stmn1), and miR-101 could bind to the 3′-untranslated region (UTR) of Stmn1 to inhibit Stmn1 translation. The inhibition of cell growth and metastasis induced by up-regulation of miR-101 was partially restored by overexpresson of Stmn1. Knockdown of Stmn1 attenuates the down-regulation of miR-101-mediated enhancement of cell growth and metastasis. More importantly, in vivo analysis found that Stmn1 mRNA and protein level in different subtypes of human breast cancer tissues, contrary to the down-regulation of miR-101, were significantly elevated. This study demonstrates that down-regulation of miR-101 in different subtypes of human breast cancer tissues is linked to the increase of cellular proliferation and invasiveness via targeting Stmn1, which highlights novel regulatory mechanism in breast cancer and may provide valuable clues for the future clinical diagnosis of breast cancer.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
4.8
作者：
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通讯作者：
Atweh, GF
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
--
作者：
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通讯作者：
Würdinger T
影响因子：
3.7
作者：
Peurala H;Greco D;Heikkinen T;Kaur S;Bartkova J;Jamshidi M;Aittomäki K;Heikkilä P;Bartek J;Blomqvist C;Bützow R;Nevanlinna H
通讯作者：
Nevanlinna H