Research Papers:

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

Xinying Xue, Yuxia Liu, Yong Wang, Mingming Meng, Kaifei Wang, Xuefeng Zang, Sheng Zhao, Xiaohua Sun, Lei Cui, Lei Pan and Sanhong Liu _

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Oncotarget. 2016; 7:84508-84519. https://doi.org/10.18632/oncotarget.13022

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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

Correspondence to:

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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PII: 13022