Leucine-rich repeat neuronal protein-1 suppresses apoptosis of gastric cancer cells through regulation of Fas/FasL.

Abstract

Gastric cancer (GC) is a common cause of cancer-related death worldwide. As a result of the lack of reliable diagnostic or prognostic biomarkers for GC, patient prognosis is still poor. Therefore, there is an urgent need for studies examining the underlying pathogenesis of GC in order to find effective biomarkers. LRRN1 (leucine-rich repeat neuronal protein-1) is a type I transmembrane protein that plays an important role in the process of nerve development and regeneration. However, its role in cancer, especially in GC, remains unclear. In the present study, we found that LRRN1 expression is upregulated in GC tissues and that high LRRN1 expression is associated with poor prognosis. siRNA and shRNA-mediated knockdowns of LRRN1 expression promoted GC cell apoptosis and activation of the Fas/FasL pathway. LRRN1 knockdown also resulted in upregulation of JUN, a subunit of the transcription factor AP-1 (activator protein-1). This suggests that LRRN1 suppresses GC cell apoptosis by downregulating AP-1, resulting in inhibition of the Fas/FasL pathway. These results confirm that LRRN1 plays a significant role in GC pathogenesis. Moreover, LRRN1 may be a potential prognostic biomarker and therapeutic target for GC.

• Authors: Bofang Liu, Ye Zhang, Yibo Fan, Shuo Wang, Zhi Li, Mingming Deng, Ce Li, Jin Wang, Rui Ma, Xiaoxun Wang, Yan Wang, Ling Xu, Kezuo Hou, Xiaofang Che, Yunpeng Liu, Xiujuan Qu
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 7 Pg. 2145-2155 (Jul 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31087525 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• FAS protein, human
• FASLG protein, human
• Fas Ligand Protein
• LRRN1 protein, human
• Membrane Proteins
• Neoplasm Proteins
• Nerve Tissue Proteins
• Transcription Factor AP-1
• fas Receptor

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Fas Ligand Protein (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• Neoplasm Proteins (genetics, metabolism)
• Neoplasm Transplantation
• Nerve Tissue Proteins
• Prognosis
• Signal Transduction
• Stomach Neoplasms (genetics, metabolism, pathology)
• Survival Analysis
• Transcription Factor AP-1 (metabolism)
• Up-Regulation
• fas Receptor (metabolism)