期刊
CANCER SCIENCE
卷 110, 期 7, 页码 2145-2155出版社
WILEY
DOI: 10.1111/cas.14042
关键词
apoptosis; Fas/FasL; gastric cancer; LRRN1; prognostic
类别
资金
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2017ZX09304025]
- Science and Technology Plan Project of Liaoning Province [2016007010]
- General Project of Liaoning Province Department of Education [LS201613]
- General Projects of Liaoning Province Colleges and Universities [LFWK201706]
- National Natural Science Foundation of China [81572374, 81602098]
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.
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