Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of let-7a in breast cancer cells.
Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of let-7a in breast cancer cells.
复制标题
Lin28 通过下调乳腺癌细胞中的 Let-7a 诱导上皮间质转化和干性。
DOI：
10.1371/journal.pone.0083083
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yu F
中科院分区：
文献类型：
--
作者：
Liu Y;Li H;Feng J;Cui X;Huang W;Li Y;Su F;Liu Q;Zhu J;Lv X;Chen J;Huang D;Yu F
众所周知，rna结合蛋白Lin28通过抑制肿瘤抑制因子let-7的生物发生而促进恶性肿瘤。然而，Lin28/let-7轴在乳腺癌上皮-间质转化（EMT）和干性中的作用尚未得到明确阐述。在我们之前的研究中，我们证明了let-7调节乳腺癌干细胞的自我更新和致瘤性。在本研究中，我们证实Lin28在间充质(M)型细胞（MDA-MB-231和sk -3）中高表达，但在上皮(E)型细胞（MCF-7和BT-474）中几乎检测不到。Lin28显著诱导EMT，提高乳腺球形成率和ALDH活性，进而促进乳腺癌细胞的集落形成、粘附和迁移。此外，我们证明了Lin28通过下调let-7a诱导乳腺癌细胞的EMT。引人注目的是，在发生转移的乳腺癌中发现了Lin28过表达，并且强烈预测了乳腺癌的不良预后。考虑到Lin28通过let-7a诱导EMT并促进乳腺癌转移，Lin28可能是根除乳腺癌转移的治疗靶点。
The RNA-binding protein Lin28 is known to promote malignancy by inhibiting the biogenesis of let-7, which functions as a tumor suppressor. However, the role of the Lin28/let-7 axis in the epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer has not been clearly expatiated. In our previous study, we demonstrated that let-7 regulates self-renewal and tumorigenicity of breast cancer stem cells. In the present study, we demonstrated that Lin28 was highly expressed in mesenchymal (M) type cells (MDA-MB-231 and SK-3rd), but it was barely detectable in epithelial (E) type cells (MCF-7 and BT-474). Lin28 remarkably induced the EMT, increased a higher mammosphere formation rate and ALDH activity and subsequently promoted colony formation, as well as adhesion and migration in breast cancer cells. Furthermore, we demonstrated that Lin28 induced EMT in breast cancer cells via downregulation of let-7a. Strikingly, Lin28 overexpression was found in breast cancers that had undergone metastasis and was strongly predictive of poor prognoses in breast cancers. Given that Lin28 induced the EMT via let-7a and promoted breast cancer metastasis, Lin28 may be a therapeutic target for the eradication of breast cancer metastasis.
登录
查看更多内容
影响因子：
4.7
作者：
McCarty, Mark F.
通讯作者：
McCarty, Mark F.
Lin28 通过调节乳腺癌细胞中的 p21、Rb 和 Let-7a miRNA 介导紫杉醇耐药性
影响因子：
3.7
作者：
Lv K;Liu L;Wang L;Yu J;Liu X;Cheng Y;Dong M;Teng R;Wu L;Fu P;Deng W;Hu W;Teng L
通讯作者：
Teng L
影响因子：
56.9
作者：
AMBROS, V;HORVITZ, HR
通讯作者：
HORVITZ, HR
影响因子：
8
作者：
Peng, S.;Maihle, N. J.;Huang, Y.
通讯作者：
Huang, Y.
影响因子：
11.2
作者：
Li Y;VandenBoom TG 2nd;Kong D;Wang Z;Ali S;Philip PA;Sarkar FH
通讯作者：
Sarkar FH