Deregulation of calcium/calmodulin-dependent protein kinase II (CAMK2) inhibitor 1 (CAMK2N1) has been reported to be associated with the development of several malignancies. To date, there have been few studies on the role of CAMK2N1 in lung cancer. This study aimed to investigate the relationship between CAMK2N1 and the progression of non-small cell lung cancer (NSCLC). Methodological quality was assessed using the ARRIVE guidelines. CAMK2N1 was expressed at low levels in NSCLC tissues. Overexpression of CAMK2N1 in NSCLC cell lines resulted in changes such as proliferation inhibition, metastasis inhibition, autophagy increase, and apoptosis. Mechanistic studies revealed the regulatory role of CAMK2N1/CAMK2 in AKT/mTOR signaling. Upregulation of CAMK2N1 decreased the expression levels of phosphorylated calmodulin kinase 2 (p-CaMK2), phosphorylated Akt (p-Akt), and phosphorylated-mTOR (p-mTOR). In contrast, CAMK2 overexpression increased p-AKT and p-mTOR levels. Inhibition of autophagy or activation of AKT signaling reduced CAMK2N1-mediated tumor suppression. The tumorigenic ability of CAMK2N1 overexpressing cells significantly diminished in nude mice. In conclusion, this study demonstrated the cancer suppressive function of CAMK2N1 in NSCLC and showed that CAMK2N1/CAMK2 exerted anti-cancer effects by inhibiting the AKT/mTOR signaling pathway to promote autophagy.

中文翻译：

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靶向CAMK2N1/CAMK2通过AKT/mTOR信号通路促进自噬和凋亡抑制非小细胞肺癌侵袭、迁移和血管生成

据报道，钙/钙调蛋白依赖性蛋白激酶 II (CAMK2) 抑制剂 1 (CAMK2N1) 的失调与多种恶性肿瘤的发生有关。迄今为止，关于CAMK2N1在肺癌中的作用的研究还很少。本研究旨在探讨CAMK2N1与非小细胞肺癌（NSCLC）进展的关系。使用 ARRIVE 指南评估方法学质量。 CAMK2N1 在 NSCLC 组织中低水平表达。 CAMK2N1在NSCLC细胞系中的过度表达导致增殖抑制、转移抑制、自噬增加和凋亡等变化。机制研究揭示了 CAMK2N1/CAMK2 在 AKT/mTOR 信号传导中的调节作用。 CAMK2N1 的上调可降低磷酸化钙调蛋白激酶 2 (p-CaMK2)、磷酸化 Akt (p-Akt) 和磷酸化 mTOR (p-mTOR) 的表达水平。相反，CAMK2 过表达增加了 p-AKT 和 p-mTOR 水平。抑制自噬或激活 AKT 信号传导可减少 CAMK2N1 介导的肿瘤抑制。 CAMK2N1过表达细胞在裸鼠中的致瘤能力显着减弱。总之，本研究证明了CAMK2N1在NSCLC中的抑癌功能，并表明CAMK2N1/CAMK2通过抑制AKT/mTOR信号通路促进自噬发挥抗癌作用。