LncRNA HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2

Long non-coding RNA HOTAIR predicts negative tumor prognosis and exhibits oncogenic activity. Herein, we demonstrate HOTAIR promotes human liver cancer stem cell malignant growth through downregulation of SETD2. Mechanistically, HOTAIR reduces the recuritment of the CREB, P300, RNA polII onto the SETD2 promoter region that inhibits SETD2 expression and its phosphorylation. Thereby, the SETD2 binding capacity to substrate histone H3 is weakened, triggering a reduction of trimethylation on histone H3 thirty-sixth lysine, and thereby the H3K36me3–hMSH2-hMSH6-SKP2 complex is also decreased. Strikingly, the complex occupancy on chromosome is depressed, preventing from mismatch DNA repair. While reducing the degradation capacity of Skp2 for aging histone H3 bound to damaged DNA, the aging histone repair is impaired. Furthermore, that the damaged DNA escaped to repair can causes microsatellite instability(MSI) and abnormal expression of cell cycle related genes that may trigger the hepatocarcinogenesis. This study provides evidence for HOTAIR to promote tumorigenesis via downregulating SETD2 in liver cancer stem cells.

• Publication year

  2015

• Venue

  OncoTarget

• Publication date

  2015-06-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.18632/oncotarget.4443PMID 26172293PMCID 4695030
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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