MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN
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Xinying Xue1,2, Yuxia Liu3, Yong Wang1, Mingming Meng4, Kaifei Wang2, Xuefeng Zang5, Sheng Zhao6, Xiaohua Sun7, Lei Cui8, Lei Pan1, Sanhong Liu9
1Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
2Department of Respiratory Diseases of Chinese PLA General Hospital, Beijing, China
3Department of Research, Peking Union Medical Collage Hospital, Beijing, China
4Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
5Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
6Department of Cardiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing, China
7Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China
8Department of Central Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
9Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China
Lei Pan, email: [email protected]
Sanhong Liu, email: [email protected]
Lei Cui, email: [email protected]
Keywords: non-small cell lung carcinoma, miR-21, miR-155, SOCS1, SOCS6
Received: July 11, 2016 Accepted: October 25, 2016 Published: November 02, 2016
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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