Systematic Analysis of Transcriptomic Profile of Renal Cell Carcinoma under Long-Term Hypoxia Using Next-Generation Sequencing and Bioinformatics

Int J Mol Sci. 2017 Dec 7;18(12):2657. doi: 10.3390/ijms18122657.


Patients with clear cell renal cell carcinoma (ccRCC) are often diagnosed with both von Hippel-Lindau (VHL) mutations and the constitutive activation of hypoxia-inducible factor-dependent signaling. In this study, we investigated the effects of long-term hypoxia in 786-O, a VHL-defective renal cell carcinoma cell line, to identify potential genes and microRNAs associated with tumor malignancy. The transcriptomic profiles of 786-O under normoxia, short-term hypoxia and long-term hypoxia were analyzed using next-generation sequencing. The results showed that long-term hypoxia promoted the ability of colony formation and transwell migration compared to normoxia. In addition, the differentially expressed genes induced by long-term hypoxia were involved in various biological processes including cell proliferation, the tumor necrosis factor signaling pathway, basal cell carcinoma and cancer pathways. The upregulated (L1CAM and FBN1) and downregulated (AUTS2, MAPT, AGT and USH1C) genes in 786-O under long-term hypoxia were also observed in clinical ccRCC samples along with malignant grade. The expressions of these genes were significantly correlated with survival outcomes in patients with renal cancer. We also found that long-term hypoxia in 786-O resulted in decreased expressions of hsa-mir-100 and hsa-mir-378 and this effect was also observed in samples of metastatic ccRCC compared to samples of non-metastatic ccRCC. These findings may provide a new direction for the study of potential molecular mechanisms associated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma; long-term hypoxia; next-generation sequencing; poor survival.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Cell Cycle Proteins
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cytoskeletal Proteins
  • Fibrillin-1 / genetics
  • Fibrillin-1 / metabolism
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • MicroRNAs / genetics
  • Neural Cell Adhesion Molecule L1 / genetics
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Oxygen / metabolism*
  • Proteins / genetics
  • Proteins / metabolism
  • Transcription Factors
  • Transcriptome*
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • AGT protein, human
  • AUTS2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • FBN1 protein, human
  • Fibrillin-1
  • MAPT protein, human
  • MicroRNAs
  • Neural Cell Adhesion Molecule L1
  • Proteins
  • Transcription Factors
  • USH1C protein, human
  • tau Proteins
  • Angiotensinogen
  • Oxygen