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MIR-300 in the imprinted DLK1-DIO3 domain suppresses the migration of bladder cancer by regulating the SP1/MMP9 pathway

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Version 2 2018-12-18, 12:45
Version 1 2018-12-10, 07:10
journal contribution
posted on 2018-12-18, 12:45 authored by Huaqing Yan, Jiangfeng Li, Yufan Ying, Haiyun Xie, Hong Chen, Xin Xu, Xiangyi Zheng

Emerging research has suggested that miRNAs play a significant role in oncogenesis and tumor progression by regulating multiple molecular pathways. Here, we investigated miR-300, which inhibited bladder cancer (BCa) migration by regulating the SP1/MMP9 pathway. miR-300, belonging to the DLK1-DIO3 miRNA cluster, is frequently expressed at lower levels in BCa tissue than in adjacent normal tissue due to DNA methylation. Reinforced expression of miR-300 significantly suppressed the migration of BCa cells. We carried out a search of online databases to predict potential targets of miR-300. Further studies determined that miR-300 directly targeted SP1 and suppressed its expression by specifically binding to its 3ʹ-untranslated region. Meanwhile, downregulated MMP9 may be the final effector of BCa cell mobility. Small interference RNAs silencing SP1 phenocopied the effects of miR-300 overexpression, while restoration of SP1 expression partially rescued the inhibition of metastasis induced by miR-300 overexpression in BCa cells. In conclusion, we unveiled a miR-300/SP1/MMP9 pathway in BCa. These findings demonstrate that miR-300 is a promising tumor suppressor in BCa.

Funding

This work was supported by grants from the National Natural Science Foundation of China (grant no. 81472375 and no. 81702500) and the Natural Science Foundation of Zhejiang Province (LQ16H160011).

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