MicroRNA-155 promotes bladder cancer growth by repressing the tumor suppressor DMTF1.
MicroRNA-155 promotes bladder cancer growth by repressing the tumor suppressor DMTF1.
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MicroRNA-155 通过抑制肿瘤抑制因子 DMTF1 促进膀胱癌生长
DOI：
10.18632/oncotarget.3755
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发表时间：
2015-06-30
期刊：
影响因子：
--
通讯作者：
Huang J
中科院分区：
文献类型：
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作者：
Peng Y;Dong W;Lin TX;Zhong GZ;Liao B;Wang B;Gu P;Huang L;Xie Y;Lu FD;Chen X;Xie WB;He W;Wu SX;Huang J
MicroRNA-155(miR-155)在人类肿瘤中表达异常。在本研究中，我们报道了miR-155在膀胱癌组织中的过度表达。我们发现miR-155在体外能促进细胞增殖，在体内能促进肿瘤的形成。MIR-155直接降低肿瘤抑制基因DMTF1的表达。膀胱癌组织中DMTF1的表达降低。与miR-155的恢复表达类似，DMTF1的敲除促进了细胞的生长和细胞周期的进展，而过表达的DMTF1挽救了miR-155的作用。此外，我们还研究了DMTF1-Arf-P53通路，发现DMTF1既有P53依赖的作用，也有P53非依赖的作用。综上所述，我们的研究结果提示miR-155在膀胱癌中具有促癌作用，部分是通过抑制DMTF1的表达来实现的。MiR-155及其新靶点DMTF1的鉴定将对膀胱癌诊断标志物的开发和治疗应用具有重要意义。
MicroRNA-155 (miR-155) is dysregulated in human cancers. In this study, we reported that miR-155 was over-expressed in bladder cancer tissues. We found that miR-155 promoted cell proliferation in vitro and tumorigenesis in vivo. MiR-155 directly reduced the expression of the tumor suppressor DMTF1. The expression of DMTF1 was decreased in bladder cancer tissues. Similar to the restoring miR-155 expression, knockdown of DMTF1 promoted cell growth and cell cycle progression, whereas DMTF1 over-expression rescued the effect of miR-155. Moreover, we investigated DMTF1-Arf-p53 pathway and found that DMTF1 worked in both p53-dependent and p53-independent manners. Taken together, our findings suggested that miR-155 functions as a tumor promoter in bladder cancer, which is partially through repressing DMTF1 expression. The identification of miR-155 and its novel target DMTF1 will be valuable in developing diagnostic markers and therapeutic applications for bladder cancer.