Ning Dou1, Dong Yang1, Shijun Yu1, Binghao Wu2, Yong Gao1, Yandong Li1,3. 1. Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. 2. Harvard Medical School, Massachusetts General Hospital, Cutaneous Biology Research Center, Charlestown, MA, USA. 3. Shanghai East Hospital, Research Center for Translational Medicine, Tongji University School of Medicine, Shanghai, China.
Abstract
OBJECTIVES: SNRPA is a protein component of U1 small nuclear ribonucleoprotein (U1 snRNP) complex, which takes part in the splicing of pre-mRNAs. Its expression and function in tumour remain unknown. Herein, we elucidated the functional contribution of SNRPA to the progression of gastric cancer (GC). MATERIALS AND METHODS: SNRPA expression was investigated in a GC tissue microarray by immunohistochemical staining. Cell proliferation was evaluated by CCK-8, colony formation and EdU incorporation assays. A mouse xenograft model was used to detect the tumourigenicity. Gene expression profiling was performed and then the potential target genes were verified by quantitative real-time PCR and western blot analyses. The functional relevance between SNRPA and its target gene was examined by cell growth assays. RESULTS: SNRPA expression was higher in tumour tissues than in matched normal gastric mucosa tissues, and it was positively correlated with the tumour size and progression. High SNRPA expression indicated poor prognosis of GC patients. Silencing SNRPA in GC cells markedly inhibited cell proliferation in vitro and tumour growth in a xenograft model, while overexpressing SNRPA exhibited opposite results. Moreover, we identified NGF (Nerve growth factor) as a downstream effector of SNRPA and further proved that NGF was crucial for SNRPA-mediated GC cell growth. CONCLUSIONS: These findings suggested that SNRPA may contribute to GC progression via NGF and could be a prognostic biomarker for GC.
OBJECTIVES:SNRPA is a protein component of U1 small nuclear ribonucleoprotein (U1 snRNP) complex, which takes part in the splicing of pre-mRNAs. Its expression and function in tumour remain unknown. Herein, we elucidated the functional contribution of SNRPA to the progression of gastric cancer (GC). MATERIALS AND METHODS:SNRPA expression was investigated in a GC tissue microarray by immunohistochemical staining. Cell proliferation was evaluated by CCK-8, colony formation and EdU incorporation assays. A mouse xenograft model was used to detect the tumourigenicity. Gene expression profiling was performed and then the potential target genes were verified by quantitative real-time PCR and western blot analyses. The functional relevance between SNRPA and its target gene was examined by cell growth assays. RESULTS:SNRPA expression was higher in tumour tissues than in matched normal gastric mucosa tissues, and it was positively correlated with the tumour size and progression. High SNRPA expression indicated poor prognosis of GC patients. Silencing SNRPA in GC cells markedly inhibited cell proliferation in vitro and tumour growth in a xenograft model, while overexpressing SNRPA exhibited opposite results. Moreover, we identified NGF (Nerve growth factor) as a downstream effector of SNRPA and further proved that NGF was crucial for SNRPA-mediated GC cell growth. CONCLUSIONS: These findings suggested that SNRPA may contribute to GC progression via NGF and could be a prognostic biomarker for GC.
Authors: Jian Zhang; Yen K Lieu; Abdullah M Ali; Alex Penson; Kathryn S Reggio; Raul Rabadan; Azra Raza; Siddhartha Mukherjee; James L Manley Journal: Proc Natl Acad Sci U S A Date: 2015-08-10 Impact factor: 11.205
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