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Long non-coding RNA growth arrest specific transcript 5 acts as a tumour suppressor in colorectal cancer by

Yuan Li1,2,3, Yan Li1,2, Shengkai Huang1,2

  • 1State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China.

Oncotarget
|January 19, 2017
PubMed

Insights

Long non-coding RNA growth arrest specific transcript 5 (GAS5) is downregulated in colorectal cancer (CRC), promoting tumor growth by increasing IL-10 and VEGF-A. Restoring GAS5 may offer a novel therapeutic strategy for CRC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) play crucial roles in human cancers.
  • The function and mechanism of lncRNA growth arrest specific transcript 5 (GAS5) in colorectal cancer (CRC) remain unclear.

Purpose of the Study:

  • To investigate the expression profile and biological role of GAS5 in CRC.
  • To elucidate the underlying molecular mechanism of GAS5 in CRC progression.

Main Methods:

  • Analysis of GAS5 expression in CRC tissues, serum, and cell lines.
  • Functional assays (e.g., knockdown, overexpression) to assess GAS5's impact on CRC cell proliferation and colony formation.
  • Investigation of signaling pathways (NF-κB, Erk1/2) and cytokine (IL-10, VEGF-A) involvement.
  • Validation in a mouse model of colitis-associated cancer (CAC).

Main Results:

  • GAS5 was significantly downregulated in CRC tissues, serum, and cell lines.
  • GAS5 downregulation promoted CRC cell proliferation and colony formation; GAS5 overexpression inhibited these processes.
  • GAS5 knockdown increased IL-10 and VEGF-A expression and secretion via NF-κB and Erk1/2 pathways.
  • Neutralizing IL-10 and VEGF-A reversed the pro-tumorigenic effects of GAS5 knockdown.
  • GAS5 expression negatively correlated with IL-10 and VEGF-A mRNA levels in CRC tissues and CAC models.

Conclusions:

  • GAS5 acts as a tumor suppressor in colorectal cancer by inhibiting IL-10 and VEGF-A.
  • The GAS5/IL-10/VEGF-A axis represents a novel mechanism in colorectal carcinogenesis.
  • GAS5 and its targeted cytokines (IL-10, VEGF-A) hold potential as therapeutic targets for CRC.
Keywords:
GAS5VEGFcolorectal cancerinterleukin-10long non-coding RNA

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