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Sci Rep. 2014 Oct 6;4:6527. doi: 10.1038/srep06527.

Reduced miR-3127-5p expression promotes NSCLC proliferation/invasion and contributes to dasatinib sensitivity via the c-Abl/Ras/ERK pathway.

Author information

1
1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2] Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated Shanghai Jiaotong University, No. 241, Huaihaixi Road, Shanghai, 200030, P.R. China [3].
2
1] Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China [2].
3
Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
4
Department of pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
5
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No.507, Zhengmin Road, Shanghai, 200433, P.R. China.
6
Departments of Gynaecology and Obstetrics, Shanghai First Maternity and Infant Health Hospital. Tongji University School of Medicine, No. 536, Changle Road, Shanghai, 200126, P.R. China.
7
Department of Thoracic Surgery, Shanghai Chest Hospital Affiliated Shanghai Jiaotong University, No. 241, Huaihaixi Road, Shanghai, 200030, P.R. China.

Abstract

miR-3127-5p is a primate-specific miRNA which is down-regulated in recurrent NSCLC tissue vs. matched primary tumor tissue (N = 15) and in tumor tissue vs. normal lung tissue (N = 177). Reduced miR-3127-5p expression is associated with a higher Ki-67 proliferation index and unfavorable prognosis in NSCLC. Overexpression of miR-3127-5p significantly reduced NSCLC cells proliferation, migration, and motility in vitro and in vivo. The oncogene ABL1 was a direct miR-3127-5p target, and miR-3127-5p regulated the activation of the Abl/Ras/ERK pathway and transactivated downstream proliferation/metastasis-associated molecules. Overexpression of miR-3127-5p in A549 or H292 cells resulted in enhanced resistance to dasatinib, an Abl/src tyrosine kinase inhibitor. miR-3127-5p expression levels were correlated with dasatinib sensitivity in NSCLC cell lines without K-Ras G12 mutation. In conclusion, miR-3127-5p acts as a tumor suppressor gene and is a potential biomarker for dasatinib sensitivity in the non-mutated Ras subset of NSCLC.

PMID:
25284075
PMCID:
PMC5377463
DOI:
10.1038/srep06527
[Indexed for MEDLINE]
Free PMC Article

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