Research Paper Volume 12, Issue 24 pp 25564—25580
TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-β-catenin signaling
- 1 Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
- 2 Xi'an Jiaotong University Press, Xi'an 710049, China
- 3 Xi'an Jiaotong University School of Medicine, Xi'an 710061, China
Received: May 15, 2020 Accepted: August 27, 2020 Published: December 2, 2020https://doi.org/10.18632/aging.104163
How to Cite
Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The Wnt/β-catenin pathway plays vital roles in diverse biological processes, including cell differentiation, proliferation, migration, and insulin sensitivity. A recent study reported that the DNA-binding transcriptional factor SIX3 is essential during embryonic development in vertebrates and capable of downregulating target genes of the Wnt/β-catenin pathway in lung cancer, indicating negative regulation of Wnt/β-catenin activation. However, regulation of the SIX3-Wnt/β-catenin pathway axis remains unknown. We measured the expression of TRIM27 and SIX3 as well as investigated whether there was a correlation between them in lung cancer tissue samples. Herein, we found that the E3 ubiquitin ligase, TRIM27, ubiquitinates, and degrades SIX3. TRIM27 induces non-small cell lung cancer (NSCLC) cell proliferation and metastasis, and the expression of β-catenin, S100P, TGFB3, and MMP-9 were significantly inhibited by SIX3. Furthermore, XAV939 is a selective β-catenin-mediated transcription inhibitor that inhibited TRIM27- and SIX3-mediated NSCLC cell proliferation, migration, and invasion. Clinically, lung tissue samples of cancer patients showed increased TRIM27 expression and decreased SIX3 expression. Taken together, these data demonstrate that TRIM27 acts as an oncogene regulating cell proliferation and metastasis in NSCLC through SIX3-β-catenin signaling.