Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Ave, 1095, Wuhan, 430030, China.
Cell Death Dis. 2021 Mar 4;12(3):244. doi: 10.1038/s41419-021-03532-y.
PNO1 has been reported to be involved in tumorigenesis, however, its role in glioma remains unexplored. In the present study, PNO1 expression in glioma from on-line databases, cDNA, and tissue microarrays was upregulated and associated with poor prognosis. PNO1 knockdown inhibits tumor cell growth and invasion both in vitro and in vivo; whereas PNO1 overexpression promoted cell proliferation and invasion in vitro. Notably, PNO1 interacted with THBS1 and the promotion of glioma by PNO1 overexpression could be attenuated or even reversed by simultaneously silencing THBS1. Functionally, PNO1 was involved in activation of FAK/Akt pathway. Moreover, overexpressing MYC increased PNO1 promoter activity. MYC knockdown decreased PNO1 and THBS1 expression, while inhibited cell proliferation and invasion. In conclusion, MYC-mediated upregulation of PNO1 contributes to glioma progression by activating THBS1/FAK/Akt signaling. PNO1 was reported to be a tumor promotor in the development and progression of glioma and may act as a candidate of therapeutic target in glioma treatment.
PNO1 已被报道参与肿瘤发生，但其在神经胶质瘤中的作用仍未被探索。在本研究中，在线数据库、cDNA 和组织微阵列中的 PNO1 表达上调，并与预后不良相关。PNO1 敲低抑制体外和体内肿瘤细胞的生长和侵袭；而 PNO1 过表达促进体外细胞增殖和侵袭。值得注意的是，PNO1 与 THBS1 相互作用，PNO1 过表达促进神经胶质瘤的作用可以通过同时沉默 THBS1 减弱甚至逆转。功能上，PNO1 参与激活 FAK/Akt 通路。此外，过表达 MYC 增加 PNO1 启动子活性。MYC 敲低降低 PNO1 和 THBS1 的表达，同时抑制细胞增殖和侵袭。总之，MYC 介导的 PNO1 上调通过激活 THBS1/FAK/Akt 信号通路促进神经胶质瘤的进展。PNO1 被报道在神经胶质瘤的发生和发展中是一种肿瘤促进剂，可能作为神经胶质瘤治疗的候选治疗靶点。
