LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

J Exp Clin Cancer Res. 2020 Nov 9;39(1):235. doi: 10.1186/s13046-020-01739-z.


Background: Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined.

Methods: Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis.

Results: MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies.

Conclusions: MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

Keywords: Competing endogenous RNA; E2F7; Hepatocellular carcinoma; Long non-coding RNAs, MYLK-AS1; VEGFR-2, miR-424-5p.

MeSH terms

  • Calcium-Binding Proteins / genetics*
  • Carcinoma, Hepatocellular / blood supply*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Disease Progression
  • E2F7 Transcription Factor / metabolism*
  • Female
  • Humans
  • Liver Neoplasms / blood supply*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Myosin-Light-Chain Kinase / genetics*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Transfection
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*


  • Calcium-Binding Proteins
  • E2F7 Transcription Factor
  • E2F7 protein, human
  • MIRN424 microrna, human
  • MicroRNAs
  • RNA, Antisense
  • RNA, Long Noncoding
  • Vascular Endothelial Growth Factor Receptor-2
  • MYLK protein, human
  • Myosin-Light-Chain Kinase