MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN.
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.
Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.|Department of Respiratory Diseases of Chinese PLA General Hospital, Beijing, China.
Xinying
X
Xue
Department of Research, Peking Union Medical Collage Hospital, Beijing, China.
Yuxia
Y
Liu
Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Yong
Y
Wang
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Mingming
M
Meng
Department of Respiratory Diseases of Chinese PLA General Hospital, Beijing, China.
Kaifei
K
Wang
Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Xuefeng
X
Zang
Department of Cardiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing, China.
Sheng
S
Zhao
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiaohua
X
Sun
Department of Central Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Lei
L
Cui
Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Lei
L
Pan
Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
Sanhong
S
Liu
D000072283:A549 Cells; D000818:Animals; D000070416:Antagomirs / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics / Q000378:metabolism; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000070416:Antagomirs; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C108944:SOCS1 protein, human; C473085:SOCS6 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase
SOCS1; SOCS6; miR-155; miR-21; non-small cell lung carcinoma