Tumor-suppressive miR-218-5p inhibits cancer cell proliferation and migration via EGFR in non-small cell lung cancer

被引:73
作者
Zhu, Kegan [1 ]
Ding, Hanying [1 ]
Wang, Wengong [2 ]
Liao, Zhicong [1 ]
Fu, Zheng [1 ]
Hong, Yeting [1 ]
Zhou, Yong [2 ]
Zhang, Chen-Yu [1 ]
Chen, Xi [1 ]
机构
[1] Nanjing Univ, Sch Life Sci,NAILS, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, State Key Lab Pharmaceut Biotechnol,Collaborat In, Nanjing 210046, Jiangsu, Peoples R China
[2] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Thorac & Cardiovasc Surg,Dept Gen Surg, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
NSCLC; miR-218-5p; EGFR; proliferation; migration; COLORECTAL-CANCER; TYROSINE KINASES; METASTATIC SITES; MICRORNAS; RESISTANCE; GROWTH; OVEREXPRESSION; EXPRESSION; RECEPTORS; CARCINOMA;
D O I
10.18632/oncotarget.8576
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lung cancer remains the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases. Recently, microRNAs (miRNAs) have been consistently demonstrated to be involved in NSCLC and to act as either tumor oncogenes or tumor suppressors. In this study, we identified a specific binding site for miR-218-5p in the 3'-untranslated region of the epidermal growth factor receptor (EGFR). We further experimentally validated miR-218-5p as a direct regulator of EGFR. We also identified an inverse correlation between miR-218-5p and EGFR protein levels in NSCLC tissue samples. Moreover, we demonstrated that miR-218-5p plays a critical role in suppressing the proliferation and migration of lung cancer cells probably by binding to EGFR. Finally, we examined the function of miR-218-5p in vivo and revealed that miR-218-5p exerts an anti-tumor effect by negatively regulating EGFR in a xenograft mouse model. Taken together, the results of this study highlight an important role for miR-218-5p in the regulation of EGFR in NSCLC and may open new avenues for future lung cancer therapies.
引用
收藏
页码:28075 / 28085
页数:11
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