Dual-specificity phosphatase 8 (DUSP8) plays an important role as a selective c-Jun N-terminal kinase (JNK) phosphatase in mitogen-activated protein kinase (MAPK) signaling. In this study, we found that DUSP8 is silenced by miR-147b in patients with lung adenocarcinoma (LUAD), which correlates with poor overall survival. Overexpression of DUSP8 resulted in a tumor-suppressive phenotype in vitro and in vivo experimental models, whereas silencing DUSP8 with a siRNA approach abrogated the tumor-suppressive properties. We found that miR-147b is a posttranscriptional regulator of DUSP8 that is highly expressed in patients with LUAD and is associated with lower survival. NanoString analysis revealed that the MAPK signaling pathway is mainly affected by overexpression of miR-147b, leading to increased proliferation and migration and decreased apoptosis in vitro. Moreover, induction of miR-147b promotes tumor progression in vitro and in vivo experimental models. Knockdown of miR-147b restored DUSP8, decreased tumor progression in vitro, and increased apoptosis via JNK phosphorylation. These results suggest that miR-147b plays a key role in regulating MAPK signaling in LUAD. The link between DUSP8 and miR-147b may provide novel approaches for the treatment of lung cancer.

双特异性磷酸酶 8 (DUSP8) 作为选择性 c-Jun N 末端激酶 (JNK) 磷酸酶在丝裂原激活蛋白激酶 (MAPK) 信号转导中发挥着重要作用。在这项研究中，我们发现肺腺癌 (LUAD) 患者中 DUSP8 被 miR-147b 沉默，这与较差的总生存率相关。 DUSP8 的过度表达导致体外和体内实验模型的肿瘤抑制表型，而用 siRNA 方法沉默 DUSP8 则消除了肿瘤抑制特性。我们发现 miR-147b 是 DUSP8 的转录后调节因子，在 LUAD 患者中高表达，并且与较低的生存率相关。 NanoString分析显示，MAPK信号通路主要受miR-147b过表达的影响，导致体外增殖和迁移增加，细胞凋亡减少。此外，miR-147b 的诱导在体外和体内实验模型中促进肿瘤进展。敲低 miR-147b 可恢复 DUSP8，在体外减少肿瘤进展，并通过 JNK 磷酸化增加细胞凋亡。这些结果表明 miR-147b 在调节 LUAD 中的 MAPK 信号传导中发挥关键作用。 DUSP8 和 miR-147b 之间的联系可能为肺癌的治疗提供新的方法。