MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN

被引:154
|
作者
Xue, Xinying [1 ,2 ]
Liu, Yuxia [3 ]
Wang, Yong [1 ]
Meng, Mingming [4 ]
Wang, Kaifei [2 ]
Zang, Xuefeng [5 ]
Zhao, Sheng [6 ]
Sun, Xiaohua [7 ,8 ]
Cui, Lei [9 ]
Pan, Lei [1 ]
Liu, Sanhong [10 ]
机构
[1] Capital Med Univ, Beijing Shijitan Hosp, Dept Special Med Treatment Resp Dis, Beijing, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Dept Resp Dis, Beijing, Peoples R China
[3] Peking Union Med Collage Hosp, Dept Res, Beijing, Peoples R China
[4] Capital Med Univ, Beijing Shijitan Hosp, Dept Gastroenterol, Beijing, Peoples R China
[5] Capital Med Univ, Beijing Shijitan Hosp, Dept Intens Care Unit, Beijing, Peoples R China
[6] Peking Univ, Beijing Shijitan Hosp, Ninth Sch Clin Med, Dept Cardiol, Beijing, Peoples R China
[7] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai, Peoples R China
[8] Shanghai Jiao Tong Univ, Sch Med, Shanghai, Peoples R China
[9] Capital Med Univ, Beijing Shijitan Hosp, Dept Cent Lab, Beijing, Peoples R China
[10] ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China
来源
ONCOTARGET | 2016年 / 7卷 / 51期
关键词
non-small cell lung carcinoma; miR-21; miR-155; SOCS1; SOCS6; TARGETING PTEN; ACQUIRED-RESISTANCE; GROWTH; EXPRESSION; PATHWAY; GENE;
D O I
10.18632/oncotarget.13022
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-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.
引用
收藏
页码:84508 / 84519
页数:12
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