Research Paper Volume 12, Issue 16 pp 16142—16154

LAIR-1 suppresses cell growth of ovarian cancer cell via the PI3K-AKT-mTOR pathway

Yan Liu1, *, , Li Ma1, *, , Fugen Shangguan2, *, , Xuena Zhao3, , Wenjie Wang3, , Zhiyue Gao3, , Huimin Zhou3, , Guiwu Qu4, , Yumei Huang5, , Jing An6, , Jiangnan Xue1, , Shude Yang7, , Qizhi Cao1,4, ,

  • 1 Department of Immunology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, Shandong, P.R. China
  • 2 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, P.R. China
  • 3 Binzhou Medical University, Yantai 264003, Shandong, P.R. China
  • 4 Anti-aging Research Institution, Binzhou Medical University, Yantai 264003, Shandong, P.R.China
  • 5 Department of Stomatology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong, P.R. China
  • 6 Division of Infectious Diseases and Global Health, School of Medicine, University of California at San Diego, La Jolla, CA 92037, USA
  • 7 School of Agriculture, Ludong University, Yantai 264025, Shandong, P.R.China
* Equal contribution

Received: August 28, 2019       Accepted: June 13, 2020       Published: July 4, 2020      

https://doi.org/10.18632/aging.103589
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Recently, over-expression of LAIR-1 has been found in some solid cancers, including ovarian cancer. The role of LAIR-1 in cancer progression needs further investigation. In this study, we identified the LAIR-1 cDNA sequence of the ovarian cancer cells HO8910. Using SKOV3 cells, we confirmed the finding from our previous study that LAIR-1 could suppress in vitro cell proliferation and cell migration. We also found LAIR-1 overexpression can induce apoptosis of SKOV3 cells. We revealed LAIR-1 suppressed cell growth by inhibiting the PI3K-AKT-mTOR axis. Moreover, the LAIR-1 antitumor activity and its mechanism were also identified in vivo. We used Co-IP assay and mass spectrometry to identify potential LAIR-1-binding proteins in LAIR-1 overexpressing SKOV3 cells. MS analysis identified 167 potentially interacting proteins. GO analyses indicated a possible involvement of LAIR-1 in mRNA processing through its interaction with some eukaryotic translation initiation factors (eIF4E1B, eIF2S3, eIF3D, eIF4G2, eIF5B) and eukaryotic translation elongation factors (eEF1A2 and eEF1B2). Our findings suggest that LAIR-1 may suppress the growth of ovarian cancer cells by serving as a modulator that suppresses PI3K-AKT-mTOR directly or regulating protein synthesis at the translational level. Our results indicate that a LAIR-1-based strategy may prevent or suppress the progression of ovarian cancer.

Abbreviations

LAIR-1: leukocyte-associated immunoglobulin-like receptor-1; Co-IP: Co-Immunoprecipitation; GO: Gene Ontology analysis; eIF: eukaryotic translation initiation factor; eEF: eukaryotic translation elongation factor.