Cutaneous malignant melanoma is one of the most lethal cutaneous malignancies. Accumulating evidence has demonstrated the potential influence of lncRNAs in biological behaviors of melanoma. Herein, we reported a novel lncRNA, lnc-PKNOX1-1, and systematically studied its functions and possible molecular mechanisms in melanoma. RT-qPCR assay showed that lnc-PKNOX1-1 was significantly decreased in melanoma cells and tissues. Low lnc-PKNOX1-1 expression was significantly correlated with invasive pathological type and Breslow thickness of melanoma. In vitro and in vivo experiments showed lnc-PKNOX1-1 dramatically inhibited melanoma cell proliferation, migration and invasion. Mechanically, protein microarray analysis suggested that IL-8 was negatively regulated by lnc-PKNOX1-1 in melanoma, which was confirmed by western blot and ELISA. Western blot analysis also showed that lnc-PKNOX1-1 could promote p65 phosphorylation at Ser536 in melanoma. Subsequent rescue assays proved IL-8 overexpression could partly reverse the tumor-suppressing function of lnc-PKNOX1-1 overexpression in melanoma cells, indicating that lnc-PKNOX1-1 suppressed the development of melanoma by regulating IL-8. Taken together, our study demonstrated the tumor-suppressing ability of lnc-PKNOX1-1 in melanoma, suggesting its potential as a novel diagnostic biomarker and therapeutic target for melanoma.

中文翻译：

---

Lnc-PKNOX1-1 通过调节 NF-κB/IL-8 轴抑制皮肤恶性黑色素瘤的肿瘤进展。

皮肤恶性黑色素瘤是最致命的皮肤恶性肿瘤之一。越来越多的证据证明了lncRNA对黑色素瘤生物学行为的潜在影响。在此，我们报道了一种新型lncRNA lnc-PKNOX1-1，并系统研究了其在黑色素瘤中的功能和可能的分子机制。RT-qPCR 检测显示，lnc-PKNOX1-1 在黑色素瘤细胞和组织中显着减少。lnc-PKNOX1-1低表达与黑色素瘤的侵袭性病理类型和Breslow厚度显着相关。体外和体内实验表明lnc-PKNOX1-1显着抑制黑色素瘤细胞的增殖、迁移和侵袭。从机械角度来看，蛋白质微阵列分析表明，IL-8 在黑色素瘤中受到 lnc-PKNOX1-1 的负向调节，这一点已通过蛋白质印迹和 ELISA 得到证实。Western blot 分析还表明，lnc-PKNOX1-1 可以促进黑色素瘤中 p65 Ser536 的磷酸化。随后的救援实验证明，IL-8过表达可以部分逆转黑色素瘤细胞中lnc-PKNOX1-1过表达的抑癌功能，表明lnc-PKNOX1-1通过调节IL-8抑制黑色素瘤的发展。综上所述，我们的研究证明了 lnc-PKNOX1-1 在黑色素瘤中的肿瘤抑制能力，表明其作为黑色素瘤的新型诊断生物标志物和治疗靶点的潜力。