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miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2
- Source :
- PLoS Genetics, Vol 14, Iss 12, p e1007790 (2018), PLoS Genetics
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.<br />Author summary We first showed downregulation of miR-3607-3p in NSCLC tissues and demonstrated that miR-3607-3p may act as an independent predictor of overall survival. Serum miR-3607-3p may be a novel marker of patients with NSCLC. We further found that miR-3607-3p possesses the potency to suppress NSCLC growth and metastasis and induce cell cycle arrest by regulating TGFBR1 and CCNE2. Importantly, agomiR-3607-3p could reduce tumor growth and lung and brain metastasis and inhibit TGFBR1 and CCNE2 protein expression. Our findings suggest that miR-3607-3p is a tumor suppressor in NSCLC and holds promise as a prognostic biomarker and potential therapeutic target for NSCLC.
- Subjects :
- Male
0301 basic medicine
Cell signaling
Cancer Research
Lung Neoplasms
Receptor, Transforming Growth Factor-beta Type I
non-small cell lung cancer (NSCLC)
Signal transduction
QH426-470
Biochemistry
Lung and Intrathoracic Tumors
Metastasis
Mice
0302 clinical medicine
Cell Movement
Carcinoma, Non-Small-Cell Lung
Basic Cancer Research
Medicine and Health Sciences
Neoplasm Metastasis
Genetics (clinical)
Cell Cycle
Signaling cascades
Animal Models
Middle Aged
Cell cycle
Prognosis
Enzymes
Nucleic acids
Oncology
Experimental Organism Systems
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Female
Oxidoreductases
Luciferase
Research Article
Cell biology
Down-Regulation
Mice, Nude
Mouse Models
Biology
Transfection
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Cell Line, Tumor
Cyclins
microRNA
Biomarkers, Tumor
Genetics
Carcinoma
medicine
Animals
Humans
RNA, Small Nucleolar
Neoplasm Invasiveness
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Aged
Cell Proliferation
Natural antisense transcripts
Biology and life sciences
Cell growth
Microarray analysis techniques
Cancers and Neoplasms
Proteins
medicine.disease
Non-Small Cell Lung Cancer
Gene regulation
respiratory tract diseases
MicroRNAs
030104 developmental biology
TGF-beta signaling cascade
Animal Studies
Enzymology
Cancer research
RNA
Ectopic expression
Gene expression
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics
- Accession number :
- edsair.doi.dedup.....f1d8223597a50ac9001ff62c27aa3760