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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.
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收藏
页码:84508 / 84519
页数:12
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