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SNORD126 promotes HCC and CRC cell growth by activating the PI3K-AKT pathway through FGFR2

Xianlong Fang1, Dongmei Yang2, Hongping Luo3

  • 1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Journal of Molecular Cell Biology
|December 4, 2016
PubMed

Insights

Small nucleolar RNA SNORD126 drives cancer growth by activating the PI3K-AKT pathway and FGFR2. Targeting SNORD126 may offer a new therapeutic strategy for hepatocellular carcinoma and colorectal cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Small nucleolar RNA (snoRNA) dysregulation is linked to cancer.
  • SNORD126, an orphan C/D box snoRNA, is encoded within the CCNB1IP1 gene.
  • Its specific role in cancer pathogenesis remains unclear.

Purpose of the Study:

  • To investigate the role of SNORD126 in hepatocellular carcinoma (HCC) and colorectal cancer (CRC).
  • To elucidate the molecular mechanisms underlying SNORD126's function in cancer development.

Main Methods:

  • Quantitative real-time PCR to assess SNORD126 expression in patient samples and cell lines.
  • Cell proliferation and tumorigenicity assays in vitro and in vivo.
  • Gene expression profiling and Western blotting to analyze pathway activation.
  • RNA interference and pharmacological inhibition to target SNORD126 and FGFR2.

Main Results:

  • SNORD126 was highly expressed in HCC and CRC tissues and promoted cell growth and tumorigenicity.
  • SNORD126 knockdown inhibited cancer cell proliferation.
  • SNORD126 overexpression activated the PI3K-AKT pathway, increasing AKT, GSK-3β, and p70S6K phosphorylation.
  • SNORD126 elevated fibroblast growth factor receptor 2 (FGFR2) expression, and targeting FGFR2 suppressed SNORD126-driven cell growth.

Conclusions:

  • SNORD126 plays an oncogenic role in HCC and CRC.
  • SNORD126 promotes cancer progression via the PI3K-AKT pathway and FGFR2.
  • SNORD126 represents a potential therapeutic target for liver and colorectal cancers.
Keywords:
CRCFGFR2HCCPI3K–AKTsmall nucleolar RNA

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