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B-Myb Mediates Proliferation and Migration of Non-Small-Cell Lung Cancer via Suppressing IGFBP3
- Source :
- International Journal of Molecular Sciences, Vol 19, Iss 5, p 1479 (2018), International Journal of Molecular Sciences; Volume 19; Issue 5; Pages: 1479, International Journal of Molecular Sciences
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- B-Myb has been shown to play an important oncogenic role in several types of human cancers, including non-small-cell lung cancer (NSCLC). We previously found that B-Myb is aberrantly upregulated in NSCLC, and overexpression of B-Myb can significantly promote NSCLC cell growth and motility. In the present study, we have further investigated the therapeutic potential of B-Myb in NSCLC. Kaplan–Meier and Cox proportional hazards analysis indicated that high expression of B-Myb is significantly associated with poor prognosis in NSCLC patients. A loss-of-function study demonstrated that depletion of B-Myb resulted in significant inhibition of cell growth and delayed cell cycle progression in NSCLC cells. Notably, B-Myb depletion also decreased NSCLC cell migration and invasion ability as well as colony-forming ability. Moreover, an in vivo study demonstrated that B-Myb depletion caused significant inhibition of tumor growth in a NSCLC xenograft nude mouse model. A molecular mechanistic study by RNA-seq analysis revealed that B-Myb depletion led to deregulation of various downstream genes, including insulin-like growth factor binding protein 3 (IGFBP3). Overexpression of IGFBP3 suppressed the B-Myb-induced proliferation and migration, whereas knockdown of IGFBP3 significantly rescued the inhibited cell proliferation and motility caused by B-Myb siRNA (small interfering RNA). Expression and luciferase reporter assays revealed that B-Myb could directly suppress the expression of IGFBP3. Taken together, our results suggest that B-Myb functions as a tumor-promoting gene via suppressing IGFBP3 and could serve as a novel therapeutic target in NSCLC.
- Subjects :
- Male
0301 basic medicine
Small interfering RNA
Lung Neoplasms
medicine.medical_treatment
IGFBP3
Cell Cycle Proteins
NSCLC
lcsh:Chemistry
Mice
0302 clinical medicine
Nude mouse
Cell Movement
Carcinoma, Non-Small-Cell Lung
RNA, Small Interfering
Extracellular Signal-Regulated MAP Kinases
Promoter Regions, Genetic
lcsh:QH301-705.5
Spectroscopy
Gene knockdown
biology
Chemistry
Cell Cycle
B-Myb
proliferation
motility
General Medicine
Prognosis
Computer Science Applications
Gene Expression Regulation, Neoplastic
Cell Transformation, Neoplastic
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Female
animal structures
Motility
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Downregulation and upregulation
Cell Line, Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Neoplasm Staging
Cell growth
Growth factor
fungi
Organic Chemistry
biology.organism_classification
respiratory tract diseases
Disease Models, Animal
Insulin-Like Growth Factor Binding Protein 3
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Trans-Activators
Cancer research
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....60cc3db7c1377ecd0a1fbc55a2f908ee