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STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells
- Title
- STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells
- Authors
- Lee H.; Chin H.; Kim H.; Jung H.; Lee D.
- Ewha Authors
- 이대기
- SCOPUS Author ID
- 이대기
- Issue Date
- 2020
- Journal Title
- Molecular Oncology
- ISSN
- 1574-7891
- Citation
- Molecular Oncology vol. 14, no. 8, pp. 1850 - 1867
- Keywords
- 4E-BP1; cross-talk; MLST8; mTORC1; STAT3
- Publisher
- John Wiley and Sons Ltd
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Signal transducer and activator of transcription 3 (STAT3) regulates cell growth, cell survival, angiogenesis, metastasis of cancer cells, and cancer immune evasion by regulating gene expression as a transcription factor. However, the effect of STAT3 on translation is almost unknown. We demonstrated that STAT3 acts as a trans-acting factor for MLST8 gene expression and the protein level of mLST8, a core component of mechanistic target of rapamycin complex 1 and 2 (mTORC1/2), positively regulates the mTORC1/2 downstream pathways. Suppression of STAT3 by siRNA attenuated 4E-BP1 phosphorylation, cap-dependent translation, and cell proliferation in a variety of cancer cells. In HCT116 cells, STAT3 knockdown-induced decreases in 4E-BP1 and AKT phosphorylation levels were further attenuated by MLST8 knockdown or recovered by mLST8 overexpression. STAT3 knockdown-induced G2/M phase arrest was partially restored by co-knockdown of 4EBP1, and the attenuation of cell proliferation was enhanced by the expression of an mTORC1-mediated phosphorylation-defective mutant of 4E-BP1. ChIP and promoter mapping using a luciferase reporter assay showed that the −951 to −894 bp of MLST8 promoter seems to include STAT3-binding site. Overall, these results suggest that STAT3-driven MLST8 gene expression regulates cap-dependent translation through 4E-BP1 phosphorylation in cancer cells. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
- DOI
- 10.1002/1878-0261.12735
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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