Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer

Ying Yang; Ziming Li; Hong Yuan; Wenxiang Ji; Kaixuan Wang; Tingting Lu; Yongfeng Yu; Qingyu Zeng; Fan Li; Weiliang Xia; Shun Lu

doi:10.1038/s41389-019-0151-1

Reciprocal regulatory mechanism between miR-214-3p and FGFR1 in FGFR1-amplified lung cancer

Oncogenesis. 2019 Sep 6;8(9):50. doi: 10.1038/s41389-019-0151-1.

Authors

Ying Yang^{1

2}, Ziming Li¹, Hong Yuan¹, Wenxiang Ji¹, Kaixuan Wang¹, Tingting Lu¹, Yongfeng Yu¹, Qingyu Zeng², Fan Li², Weiliang Xia³, Shun Lu⁴

Affiliations

¹ Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, 20030, Shanghai, China.
² School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Huashan Road 1954, 200030, Shanghai, China.
³ School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Huashan Road 1954, 200030, Shanghai, China. wlxia@sjtu.edu.cn.
⁴ Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, West Huaihai Road 241, 20030, Shanghai, China. shunlu@sjtu.edu.cn.

Abstract

MicroRNA (miRNA) and fibroblast growth factor receptor 1 (FGFR1) dysregulation are considered to play an important role in tumor proliferation, invasion, and metastasis. However, the regulatory mechanism between miRNAs and FGFR1 in lung cancer remains unclear and extremely critical. miR-214-3p was sharply decreased and showed a significantly negative correlation with FGFR1 in lung cancer patients (n = 30). Luciferase reporter assay confirmed that miR-214-3p could downregulate FGFR1 by directly targeting 3'-untranslated region (UTR). miR-214-3p inhibited the processes of epithelial-mesenchymal transition and Wnt/MAPK/AKT (Wnt/mitogen-activated protein kinase/AKT) signaling pathway by targeting FGFR1. Moreover, miR-214-3p not only established a negative feedback regulation loop with FGFR1 through ERK (extracellular signal-regulated kinase) but also developed a synergism with FGFR1 inhibitor AZD4547. In conclusion, our study demonstrated the regulatory mechanism between miR-214-3p and FGFR1 in lung cancer. miR-214-3p acts as a vital target in FGFR1-amplified lung cancer by forming a miR-214-3p-FGFR1-Wnt/MAPK/AKT signaling pathway network. Co-targeting miR-214-3p and FGFR1 could provide greater benefits to patients with FGFR1-amplified lung cancer.