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Estrogen receptor β promotes the vasculogenic mimicry (VM) and cell invasion via altering the lncRNA-MALAT1/miR-145-5p/NEDD9 signals in lung cancer

Oncogene volume 38, pages 1225–1238 (2019)Cite this article

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Abstract

While estrogen receptor β (ERβ) may impact the progression of non-small cell lung cancer (NSCLC), its linkage to alteration of the vasculogenic mimicry (VM) formation to influence the NSCLC cell invasion remains unclear. Here, we analyzed immunohistochemistry data from NSCLC tissues and found that ERβ-positive NSCLC female patients had worse survival outcomes than those of ERβ-negative NSCLC female patients. In vitro studies using multiple NSCLC cell lines also revealed that ERβ could increase the VM formation and cell invasion. Molecular mechanism dissection suggested that ERβ could increase the lncRNA-MALAT1 (MALAT1) expression via directly binding to the estrogen response elements (EREs) located on the promoter of MALAT1, which could then lead to (i) suppressing the miR145-5p and (ii) increasing the NEDD9 protein expression as miR145-5p can directly target the 3ʹ-UTR of NEDD9-mRNA. A preclinical study using the in vivo mouse model further confirmed the in vitro cell lines data. Together, results from the above studies demonstrated that ERβ can promote NSCLC VM formation and cell invasion via altering the ERβ/MALAT1/miR145-5p/NEDD9 signaling. Targeting this newly identified signaling pathway with small molecules may help the development of novel therapies to better suppress the NSCLC metastasis.

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Acknowledgements

This work was partially supported by George Whipple Professorship Endowment. We thank Karen Wolf for assistance in manuscript preparation.

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    Authors and Affiliations

    1. General Department of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

      Weiwei Yu, Yuan Chen & Cuntai Zhang

    2. George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY, 14642, USA

      Weiwei Yu, Jie Ding, Maio He, Yuan Chen, Ronghao Wang, Zhenwei Han, Emily Z. Xing, Cuntai Zhang & Shuyuan Yeh

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    Yu, W., Ding, J., He, M. et al. Estrogen receptor β promotes the vasculogenic mimicry (VM) and cell invasion via altering the lncRNA-MALAT1/miR-145-5p/NEDD9 signals in lung cancer. Oncogene 38, 1225–1238 (2019). https://doi.org/10.1038/s41388-018-0463-1

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