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

  • Aging (Albany NY). 2020 Sep 5;12(16):16142-16154. doi: 10.18632/aging.103589.
Yan Liu  1  2 Li Ma  1  2 Fugen Shangguan  3  2 Xuena Zhao  4 Wenjie Wang  4 Zhiyue Gao  4 Huimin Zhou  4 Guiwu Qu  5 Yumei Huang  6 Jing An  7 Jiangnan Xue  1 Shude Yang  8 Qizhi Cao  1  5
Affiliations
  • 1. Department of Immunology, School of Basic Medical Sciences, Binzhou Medical University, Yantai 264003, Shandong, P.R. China.
  • 2. Equal contribution.
  • 3. 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.
  • 4. Binzhou Medical University, Yantai 264003, Shandong, P.R. China.
  • 5. Anti-aging Research Institution, Binzhou Medical University, Yantai 264003, Shandong, P.R.China.
  • 6. Department of Stomatology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong, P.R. China.
  • 7. Division of Infectious Diseases and Global Health, School of Medicine, University of California at San Diego, La Jolla, CA 92037, USA.
  • 8. School of Agriculture, Ludong University, Yantai 264025, Shandong, P.R.China.
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.

Keywords
LAIR-1; PI3K-AKT-mTOR pathway; cell proliferation; eEF1A2; ovarian cancer.
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