The LncRNA MIR155HG is Upregulated by SP1 in Melanoma Cells and Drives Melanoma Progression via Modulating the MiR-485-3p/PSIP1 Axis

Anticancer Agents Med Chem. 2022;22(1):152-159. doi: 10.2174/1871520621666210322092906.

Abstract

Background: MIR155HG is a long non-coding RNA (lncRNA) that has been shown to be dysregulated in a range of tumor types, but the functions of this lncRNA in melanoma remain to be explored.

Objectives: We explored the functions of lncRNA MIR155HG in melanoma progression.

Methods: The expression of miR155HG was analyzed in clinical melanoma. Bioinformatics analysis was performed to assess the potential tumor-related functions of miR155HG. The interaction of miR155HG and SP1 and the inhibition of PSIP1 by miR-485-3p were analyzed by ChIP, luciferase reporter experiments, and the biological effects in melanoma were explored by colony formation assays, EdU cell proliferation assays, Transwell analysis, and intracranial melanoma mouse model.

Results: Herein, we found that MIR155HG was markedly upregulated in melanoma cell lines and tissues. We further determined that the SP1 transcription factor was responsible for driving MIR155HG upregulation in melanoma. Elevated MIR155HG levels were linked to decreased overall survival (OS) in melanoma patients, and we further determined that MIR155HG expression was an independent predictor of melanoma patient prognosis. When MIR155HG was knocked down in melanoma cells, this impaired their proliferative, migratory, and invasive activity. By using predictive bioinformatics analyses, we identified miR-485-3p as a microRNA (miRNA) capable of binding to both MIR155HG and the 3' UTR of PSIP1.

Conclusion: Together, these results suggest that MIR155HG is capable of promoting melanoma cell proliferation via the miR-485-3p/PSIP1 axis. These novel findings provide new insights into the development of melanoma, potentially highlighting future avenues for therapeutic intervention.

Keywords: MIR155HG; Melanoma; PSIP1; SP1; miR-485-3p; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Software
  • Sp1 Transcription Factor / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation*

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN485 microRNA, human
  • MicroRNAs
  • PSIP1 protein, human
  • RNA, Long Noncoding
  • Sp1 Transcription Factor
  • SP1 protein, human
  • Transcription Factors