Molecular interplay between linc01134 and YY1 dictates hepatocellular carcinoma progression

J Exp Clin Cancer Res. 2020 Apr 9;39(1):61. doi: 10.1186/s13046-020-01551-9.


Background: Revealing the mechanical role of long non-coding RNAs (lncRNAs) in tumorigenesis can contribute to novel therapeutic target for cancers. The regulatory role of linc01134 in hepatocellular carcinoma (HCC) has not been studied yet.

Materials and methods: qRT-PCR and western blot were conducted to measure relevant RNA and protein expressions. CCK-8, colony formation, EdU, flow cytometry, wound-healing, transwell assays and xenograft experiments were performed to determine the role of linc01134 in HCC. ChIP and luciferase reporter assays were performed to analyze the effects of Yin Yang-1 (YY1) on linc01134 transcription activity. Relevant mechanical experiments were performed to verify interaction between relative genes.

Results: YY1 enhanced linc01134 transcription by interacting with linc01134 promoter. Knockdown of linc01134 inhibited proliferation, migration and epithelial-mesenchymal transition (EMT), yet promoting apoptosis in HCC cells. Mechanically, linc01134 acted as miR-324-5p sponge and interacted with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to increase the stability of YY1 mRNA expression. Up-regulated YY1 continuously stimulated linc01134 expression by enhancing linc01134 promoter activity, forming a positive feedback loop.

Conclusion: Linc01134/miR-324-5p/IGF2BP1/YY1 feedback loop mediates HCC progression, which possibly provide prognosis and treatment target of HCC.

Keywords: Hepatocellular carcinoma; IGF2BP1; YY1; linc01134.

MeSH terms

  • Animals
  • Carcinogenesis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Disease Progression
  • Hep G2 Cells
  • Heterografts
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transfection


  • Cell Cycle Proteins
  • RNA, Long Noncoding
  • Transcription Factors
  • YY1AP1 protein, human