过氧化物酶体增殖物激活受体
基因敲除
下调和上调
受体
过氧化物酶体
癌症研究
细胞生长
内科学
癌变
内分泌学
免疫组织化学
癌症
化学
医学
细胞凋亡
生物化学
基因
作者
Tingting Cao,Song Wang,Long Qian,Chengwei Wu,Tao Huang,Ye Wang,Qian Li,Jiawei Wang,Yabin Xia,Li Xu,Luman Wang,Xiaoxu Huang
标识
DOI:10.1016/j.tranon.2023.101734
摘要
Among cancers, gastric cancer (GC) ranks third globally in morbidity and mortality, particularly in East Asia. Natriuretic peptide receptor A (NPRA), a receptor for guanylate cyclase, plays important roles in regulating water and sodium balance. Recent studies have suggested that NPRA is involved in tumorigenesis, but its role in GC development remains unclear. Herein, we showed that the expression level of NPRA was positively correlated with gastric tumor size and clinical stage. Patients with high NPRA expression had a lower five-year survival rate than those with low expression, and NPRA was identified as an independent predictor of GC prognosis. NPRA knockdown suppressed GC cell proliferation, migration and invasion. NPRA overexpression enhanced cell malignant behavior. Immunohistochemistry of collected tumor samples showed that tumors with high NPRA expression had higher peroxisome proliferator-activated receptor α (PPARα) levels. In vivo and in vitro studies showed that NPRA promotes fatty acid oxidation and tumor cell metastasis. Co-IP showed that NPRA binds to PPARα and prevents PPARα degradation. PPARα upregulation under NPRA protection activates arnitine palmitoyl transferase 1B (CPT1B) to promote fatty acid oxidation. In this study, new mechanisms by which NPRA promotes the development of GC and new regulatory mechanisms of PPARα were identified.
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