TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000424848
  • Gene Name:CDK6
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:hypopharyngeal squamous cell carcinoma
  • Tissue:FaDu (derived from a primary lesion of hypopharyngeal SCC), SAS (derived from a primary lesion of tongue SCC), HSC3 (derived from lymph node metastasis of tongue SCC), HCT116 p53+/+ (derived from a colon adenocarcinoma) and its p53-/- derivative

Other information

  • Title:microRNA-504 inhibits cancer cell proliferation via targeting CDK6 in hypopharyngeal squamous cell carcinoma.
  • Journal:Int J Oncol
  • Published:2014
  • PubMed ID:24647829
  • Abstract:Our recent study of the microRNA (miRNA) expression signature of hypopharyngeal squamous cell carcinoma (HSCC) revealed that microRNA-504 (miR-504) is significantly downregulated in HSCC tissues, suggesting that this miRNA is a candidate tumor suppressor. However, several previous reports indicated that miR-504 has an oncogenic function through targeting TP53. The aim of this study was to investigate the functional significance of miR-504 in cancer cells and to identify novel targets regulated by this miRNA in HSCC cells. First, we confirmed the downregulation of miR-504 in HSCC clinical specimens (P<0.0001) by qPCR. Using two sources of miR-504 to restore function, we observed significant inhibition of cancer cell proliferation in head and neck SCC (HNSCC) cell lines (FaDu, SAS and HSC3) and HCT116 colon carcinoma cells (p53+/+ and p53-/-). In HNSCC cells, induction of cell cycle arrest was observed by miR-504 transfection. To identify the molecular targets of miR-504, we performed gene expression analysis of miR-504 transfectants and in silico database analyses. Our data showed that cell cycle-related genes (RB1, CDK6, CDC23 and CCND1) were candidate target genes of miR-504. In HSCC clinical specimens, the expression of cyclin-dependent kinase 6 (CDK6) was significantly higher in cancer tissues compared to non-cancer tissues (P=0.0004). A significant inverse correlation between CDK6 and miR-504 expression was found (r=-0.43, P=0.0039). Expression of miR-504 inhibited CDK6 expression in HNSCC cells. Loss of tumor-suppressive miR-504 enhanced HSCC cell proliferation through targeting CDK6. The identification of novel tumor-suppressive miR-504-mediated molecular pathways and targets provide new insights into HSCC oncogenesis.
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