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miR-183-5p overexpression orchestrates collective invasion in salivary adenoid cystic carcinoma through the FAT1/YAP1 signaling pathway.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 May 07; Vol. 655, pp. 127-137. Date of Electronic Publication: 2023 Mar 08. - Publication Year :
- 2023
-
Abstract
- The invasion of cancer cells into interstitial tissues in a cohesive unit is termed collective invasion, and it is important for the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). However, the underlying mechanisms regulating SACC collective invasion are still poorly understood. Here, we found that SACC tissues exhibited remarkable FAT1 downregulation and YAP1 upregulation at the invasive front, which was closely associated with collective invasion and distant metastasis. Decreasing FAT1 expression significantly activated the YAP1 signaling pathway and promoted collective invasion. Moreover, miR-183-5p was identified as the candidate regulator of FAT1 by bioinformatic analysis and an online database algorithm. A dual luciferase reporter experiment further confirmed that miR-183-5p directly targeted the FAT1 3'-UTR to reduce FAT1 expression. Increasing or decreasing miR-183-5p expression promoted or attenuated collective invasion, which was reversed by YAP1 siRNA or FAT1 siRNA, respectively. In addition, knocking down miR-183-5p reduced tumor burden and attenuated collective invasion in vivo. Together, these results suggest that the miR-183-5p/FAT1/YAP1 signaling pathway is a critical driver of SACC collective invasion, revealing a novel therapeutic target.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023. Published by Elsevier Inc.)
- Subjects :
- Humans
Neoplasm Invasiveness genetics
Signal Transduction
RNA, Small Interfering
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Cell Movement genetics
Cell Proliferation
Cadherins metabolism
Carcinoma, Adenoid Cystic metabolism
MicroRNAs genetics
MicroRNAs metabolism
Salivary Gland Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 655
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 36934588
- Full Text :
- https://doi.org/10.1016/j.bbrc.2023.03.015