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miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Feb 25; Vol. 117 (8), pp. 4347-4357. Date of Electronic Publication: 2020 Feb 10. - Publication Year :
- 2020
-
Abstract
- Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Animals
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Carcinoma, Non-Small-Cell Lung physiopathology
Cell Line, Tumor
Cell Proliferation
Disease Progression
Down-Regulation
Female
GATA6 Transcription Factor metabolism
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
Lung Neoplasms physiopathology
Mice
Mice, Nude
MicroRNAs genetics
Tetraspanins metabolism
Xenograft Model Antitumor Assays
Carcinoma, Non-Small-Cell Lung metabolism
GATA6 Transcription Factor genetics
Lung Neoplasms metabolism
MicroRNAs metabolism
Tetraspanins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32041891
- Full Text :
- https://doi.org/10.1073/pnas.1917531117