Zhang Jia, Zhao Zhilong, Wang Jiansheng
Department of Thoracic Surgery 2, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
World J Surg Oncol. 2014 Jun 3;12:174. doi: 10.1186/1477-7819-12-174.
The receptor for the cardiac hormone atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPR-A), has been reported to be expressed in lung cancer, prostate cancer and ovarian cancer. NPR-A expression and signaling is important for tumor growth; its deficiency protects C57BL/6 mice from lung, skin and ovarian cancers. This suggests that NPR-A is a new marker and a new target for cancer therapy. Recently, NPR-A has been demonstrated to be expressed in pre-implantation embryos and in embryonic stem cells, which has a novel role in the maintenance of self-renewal and pluripotency of embryonic stem cells. A nanoparticle-formulated interfering RNA for NPR-A attenuated B16 melanoma tumors in mice. Ectopic expression of a plasmid encoding NP73-102, the NH2-terminal peptide of the ANP prohormone which downregulates NPR-A expression, also suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1 cells in immunocompetent BALB/c mice. These results suggest that NPR-A is involved in tumorigenesis and a new target for cancer therapy. This review focuses on structure, abnormal functions and carcinogenic mechanisms of NPR-A to investigate its role in tumorigenesis.
心脏激素心房利钠肽（ANP）的受体，利钠肽受体A（NPR-A），已被报道在肺癌、前列腺癌和卵巢癌中表达。NPR-A的表达和信号传导对肿瘤生长很重要；其缺失可保护C57BL/6小鼠免受肺癌、皮肤癌和卵巢癌的侵害。这表明NPR-A是一种新的癌症治疗标志物和新靶点。最近，已证明NPR-A在植入前胚胎和胚胎干细胞中表达，其在维持胚胎干细胞的自我更新和多能性方面具有新作用。一种纳米颗粒制剂的NPR-A干扰RNA可减轻小鼠B16黑色素瘤肿瘤。编码NP73-102（ANP前体激素的NH2末端肽，可下调NPR-A表达）的质粒的异位表达，也抑制了裸鼠中A549细胞的肺转移以及免疫活性BALB/c小鼠中1号线细胞的肿瘤发生。这些结果表明NPR-A参与肿瘤发生，是癌症治疗的新靶点。本综述聚焦于NPR-A的结构、异常功能和致癌机制，以研究其在肿瘤发生中的作用。
