Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis

J Cancer Res Clin Oncol. 2018 Mar;144(3):531-542. doi: 10.1007/s00432-018-2582-z. Epub 2018 Jan 19.

Abstract

Purpose: lncRNA H19 has been considered as an oncogenic lncRNA in many human tumours. In the present study, we identify the role and molecular mechanism of lncRNA H19 in melanoma.

Method: QRT-PCR was used to detect the expression of lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8), representative metabolites analysis was used to explore the biological function of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the molecular mechanism of lncRNA H19 in melanoma. We further test the function of lncRNA H19 in vivo though Xenograft tumour assay.

Results: We found that lncRNA H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and growth. We also demonstrated that lncRNA H19 may function as the sponge of miR-106a-5p to up-regulate E2F3 expression, and consequently promote the glucose metabolism and growth of melanoma.

Conclusions: This result elucidates a new mechanism for lncRNA H19 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients.

Keywords: E2F3; Glucose metabolism; LncRNA H19; Melanoma; MiR-106a-5p.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Carbohydrate Metabolism / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • E2F3 Transcription Factor / genetics
  • E2F3 Transcription Factor / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism*
  • Humans
  • Male
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Middle Aged
  • RNA, Long Noncoding / physiology*
  • Signal Transduction / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology

Substances

  • E2F3 Transcription Factor
  • E2F3 protein, human
  • H19 long non-coding RNA
  • MIRN106 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Glucose