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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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