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Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells

Deng-Chyang Wu1,2,3,4, Sophie S W Wang1,2, Chung-Jung Liu1,2

  • 1Division of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Stem Cells (Dayton, Ohio)
|August 8, 2017
PubMed

Insights

Reprogramming gastric cancer cells into induced pluripotent stem-like cells (iPSLCs) switches off oncogenic BMP7 expression. This involves the HOXA13 protein interacting with different long noncoding RNAs (lncRNAs) to regulate BMP7, inhibiting tumorigenesis.

Area of Science:

  • Cancer Biology
  • Stem Cell Biology
  • Epigenetics

Background:

  • Reprogramming cancer cells into induced pluripotent stem cells (iPSCs) offers a strategy to inhibit oncogenesis.
  • The homeobox protein HOXA13 and long noncoding RNAs (lncRNAs) play roles in this process.
  • Bone morphogenetic protein 7 (BMP7) expression is altered during cancer cell reprogramming.

Purpose of the Study:

  • To investigate the axis of lncRNAs and HOXA13 in regulating BMP7 during gastric cancer cell reprogramming.
  • To understand the epigenetic mechanisms controlling BMP7 expression in cancer cells versus iPS-like cells (iPSLCs).

Main Methods:

  • Analysis of HOXA13 recruitment to the BMP7 promoter in gastric cancer cells and iPSLCs.
  • Investigating the role of lncRNA HoxA transcript at the distal tip (HOTTIP) and lncRNA HoxA transcript antisense RNA (HOTAIR) in BMP7 regulation.
  • Utilizing knockdown experiments to assess the functional impact of HOTTIP and HOTAIR.
  • Examining epigenetic modifications, specifically trimethylation of lysine 4 on histone H3.

Main Results:

  • In gastric cancer cells, HOXA13, HOTTIP, and epigenetic modifiers activate BMP7 expression.
  • In iPSLCs, HOXA13, HOTAIR, and other epigenetic modifiers inhibit BMP7 expression.
  • HOTTIP positively regulates HOXA13-mediated BMP7 expression in cancer cells, while HOTAIR negatively regulates it in iPSLCs.

Conclusions:

  • The interaction of HOXA13 with HOTTIP or HOTAIR at distinct BMP7 promoter sites is critical for gastric cell oncogenesis and reprogramming.
  • Reprogramming gastric cancer cells using specific factors can inhibit tumorigenesis by downregulating BMP7.
Keywords:
Bone morphogenetic protein 7Gastric cancerHOXA13HoxA transcript antisense RNAHoxA transcript at the distal tipJun dimerization protein 2Long noncoding RNAOctamer-binding protein 4iPS-like cells

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