Department of Thoracic Surgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
Biosci Biotechnol Biochem. 2022 Feb 24;86(3):340-350. doi: 10.1093/bbb/zbab217.
NXPH4 is discovered to be a neuropeptide-like glycoprotein, belonging to the Neurexophilins (Nxphs) family. NXPH4 shares a similar domain structure with NXPH1, which, however, is poorly understood in terms of its function. Bioinformatics analysis and experimental verification in this study confirmed the abnormal high expression of NXPH4 in non-small cell lung cancer (NSCLC) tissues and cells. Knockdown of NXPH4 by siRNA can inhibit the proliferation and migration of cells, resulting in significant cell cycle arrest in S1 phase. Furthermore, in NSCLC cells, NXPH4 was regulated by transcriptional activation of enhancer of zeste homolog 2 (EZH2) in its upstream. While downstream, NXPH4 could interact with CDKN2A and downregulate its protein stability, thus participating in the cell cycle regulation through interacting with cyclinD-CDK4/6-pRB-E2F signaling pathway. To sum up, the present study reveals a regulatory pathway of EZH2/NXPH4/CDKN2A in NSCLC, providing possible reference for understanding the function of NXPH4 in tumors.
NXPH4 被发现是一种神经肽样糖蛋白，属于 Neurexophilins（Nxphs）家族。NXPH4 与 NXPH1 具有相似的结构域，但就其功能而言，其功能尚不清楚。本研究中的生物信息学分析和实验验证证实，NXPH4 在非小细胞肺癌（NSCLC）组织和细胞中异常高表达。通过 siRNA 敲低 NXPH4 可以抑制细胞的增殖和迁移，导致 S1 期细胞周期明显停滞。此外，在 NSCLC 细胞中，NXPH4 在上游被增强子结合蛋白 2（EZH2）的转录激活所调控。而在下游，NXPH4 可以与 CDKN2A 相互作用并降低其蛋白稳定性，从而通过与周期蛋白 D-CDK4/6-pRB-E2F 信号通路相互作用参与细胞周期调控。综上所述，本研究揭示了 NSCLC 中 EZH2/NXPH4/CDKN2A 的调控途径，为了解 NXPH4 在肿瘤中的功能提供了可能的参考。
