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

Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print Cited Medium: Internet ISSN: 1460-2180 (Electronic) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE

Publication: Oxford : Irl Press At Oxford University Press
Original Publication: [New York, IRL Press]

Melanoma*/genetics ; RNA, Long Noncoding*/metabolism ; Skin Neoplasms*/genetics; Humans ; Cell Line, Tumor ; Cell Proliferation/genetics ; Homeodomain Proteins ; Interleukin-8/genetics ; Melanoma, Cutaneous Malignant ; NF-kappa B

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.
(© The Author(s) 2023. Published by Oxford University Press.)

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81872216 National Natural Science Foundation of China; 2022YFC2504700 National Key Research and Development Program of China

0 (Homeodomain Proteins)
0 (Interleukin-8)
0 (NF-kappa B)
0 (PKNOX1 protein, human)
0 (RNA, Long Noncoding)
0 (CXCL8 protein, human)

Date Created: 20231016 Date Completed: 20240201 Latest Revision: 20241023

20241023

PMC10818096

10.1093/carcin/bgad073

37843471