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长链非编码 RNA-PKNOX1-1 通过调控 NF-κB/IL-8 轴抑制皮肤恶性黑素瘤的肿瘤进展。

Lnc-PKNOX1-1 inhibits tumor progression in cutaneous malignant melanoma by regulating NF-κB/IL-8 axis.

机构信息

Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Department of Dermatology, the First Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Carcinogenesis. 2023 Dec 30;44(12):871-883. doi: 10.1093/carcin/bgad073.

DOI:10.1093/carcin/bgad073
PMID:37843471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10818096/
Abstract

Cutaneous malignant melanoma is one of the most lethal cutaneous malignancies. Accumulating evidence has demonstrated the potential influence of long non-coding RNAs (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. Reverse transcription-quantitative PCR 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 interleukin-8 (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.

摘要

皮肤恶性黑色素瘤是最致命的皮肤恶性肿瘤之一。越来越多的证据表明，长非编码 RNA（lncRNA）在黑色素瘤的生物学行为中具有潜在影响。在此，我们报道了一个新的 lncRNA，lnc-PKNOX1-1，并系统地研究了其在黑色素瘤中的功能和可能的分子机制。逆转录定量 PCR 检测显示，lnc-PKNOX1-1 在黑色素瘤细胞和组织中显著降低。低表达 lnc-PKNOX1-1 与黑色素瘤的侵袭性病理类型和 Breslow 厚度显著相关。体外和体内实验表明，lnc-PKNOX1-1 显著抑制黑色素瘤细胞的增殖、迁移和侵袭。机制上，蛋白质微阵列分析表明，白细胞介素-8（IL-8）在黑色素瘤中受 lnc-PKNOX1-1 的负调控，这通过 Western blot 和 ELISA 得到了证实。Western blot 分析还表明，lnc-PKNOX1-1 可以促进黑色素瘤中 p65 丝氨酸 536 的磷酸化。随后的挽救实验证明，IL-8 的过表达可以部分逆转 lnc-PKNOX1-1 过表达对黑色素瘤细胞的肿瘤抑制功能，表明 lnc-PKNOX1-1 通过调节 IL-8 抑制黑色素瘤的发展。总之，我们的研究表明 lnc-PKNOX1-1 在黑色素瘤中具有肿瘤抑制能力，表明其作为黑色素瘤新型诊断标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/b51013e7f81c/bgad073_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/27d9c6e55b5b/bgad073_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/fceff7d37343/bgad073_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/917b6071204d/bgad073_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/1ba46d1f0bdd/bgad073_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/0a24a7432cdb/bgad073_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/b51013e7f81c/bgad073_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/27d9c6e55b5b/bgad073_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/fceff7d37343/bgad073_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/917b6071204d/bgad073_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/1ba46d1f0bdd/bgad073_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/0a24a7432cdb/bgad073_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c10/10818096/b51013e7f81c/bgad073_fig5.jpg

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Cutaneous melanoma.皮肤黑素瘤。
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