MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.
MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells.
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DOI：
10.18632/oncotarget.2157
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Sakuragi N
中科院分区：
文献类型：
--
作者：
Konno Y;Dong P;Xiong Y;Suzuki F;Lu J;Cai M;Watari H;Mitamura T;Hosaka M;Hanley SJ;Kudo M;Sakuragi N
MicroRNA-101在人类肿瘤中被认为是一种肿瘤抑制miRNA。然而，其在子宫内膜癌进展中的潜在功能影响和潜在机制尚未确定。在这里，我们报告说，在侵袭性子宫内膜癌细胞中，microRNA-101的重新表达导致细胞增殖抑制和诱导凋亡和衰老。microRNA-101的异位过表达减弱了上皮-间质转化相关的癌细胞迁移和侵袭，消除了球体形成能力并增强了对紫杉醇的化学敏感性。基于算法和微阵列的策略识别潜在的microRNA-101靶标。其中，我们验证了EZH 2、MCL-1和FOS作为miR-101的直接靶标，并且这些基因的沉默模拟了在促进microRNA-101功能方面观察到的肿瘤抑制作用。重要的是，进一步的结果表明，在EC标本中，低miR-101与高EZH 2、MCL-1和FOS表达之间呈负相关。我们的结论是，作为一个重要的肿瘤抑制因子，microRNA-101通过调节多个关键癌基因抑制侵袭性子宫内膜癌细胞的细胞增殖，侵袭性和自我更新。microRNA-101-EZH 2/MCL-1/FOS轴是子宫内膜癌潜在的治疗靶点。
MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/FOS axis is a potential therapeutic target for endometrial cancer.
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DOI：
10.1097/igc.0b013e318296a265
发表时间：
2013-07
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
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作者：
Eskander RN;Ji T;Huynh B;Wardeh R;Randall LM;Hoang B
通讯作者：
Hoang B
影响因子：
11.5
作者：
Chase, Andrew;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.
影响因子：
5.7
作者：
Hiroki, Eri;Akahira, Jun-ichi;Yaegashi, Nobuo
通讯作者：
Yaegashi, Nobuo
MiR-26a 通过抑制 MCL-1 抑制乳腺癌的增殖和迁移。
影响因子：
3.7
作者：
Gao J;Li L;Wu M;Liu M;Xie X;Guo J;Tang H;Xie X
通讯作者：
Xie X
影响因子：
37.3
作者：
Dong, Peixin;Xu, Zhujie;Feng, Youji
通讯作者：
Feng, Youji