A LHFPL3-AS1/miR-580-3p/STAT3 Feedback Loop Promotes the Malignancy in Melanoma via Activation of JAK2/STAT3 Signaling

Mol Cancer Res. 2020 Nov;18(11):1724-1734. doi: 10.1158/1541-7786.MCR-19-1046. Epub 2020 Aug 4.

Abstract

Melanoma is one of the severe skin cancers, accounting for three fourths of all deaths caused by skin cancers and gathering attention from researchers. Previous studies have elucidated that long noncoding RNAs (lncRNA) engage actively in tissue physiology and disease development, especially in tumorigenesis. LncRNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) has rarely been mentioned in researches regarding cancers; therefore, the underlying role and function of LHFPL3-AS1 in melanoma arouse our interest. Data from our work suggested that LHFPL3-AS1 expression was markedly elevated in melanoma tissues and cells. Of note, patients with melanoma with high level of LHFPL3-AS1 were burdened with unfavorable prognosis. Functionally, it has been revealed that LHFPL3-AS1 exerted pro-growth, pro-invasion, and pro-EMT functions in melanoma. Mechanistically, it was figured out that LHFPL3-AS1 could be transcriptionally activated by STAT3. In turn, LHFPL3-AS1 served as a sponge of miR-580-3p to augment STAT3 expression, resulting in activated JAK2/STAT3 signaling pathway in melanoma. IMPLICATIONS: Our study revealed a novel positive feedback loop LHFPL3-AS1/miR-580-3p/STAT3 in melanoma, which might contribute to finding potential therapeutic targets for melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Janus Kinase 2 / metabolism*
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Prognosis
  • STAT3 Transcription Factor / metabolism*
  • Transfection

Substances

  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 2