Journal of Translational Medicine (Mar 2021)

Hypermethylation of heparanase 2 promotes colorectal cancer proliferation and is associated with poor prognosis

  • Hui Zhang,
  • Chenxin Xu,
  • Chen Shi,
  • Junying Zhang,
  • Ting Qian,
  • Zhuo Wang,
  • Rong Ma,
  • Jianzhong Wu,
  • Feng Jiang,
  • Jifeng Feng

DOI
https://doi.org/10.1186/s12967-021-02770-0
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 13

Abstract

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Abstract Background The epigenetic abnormality of tumor-associated genes contributes to the pathogenesis of colorectal carcinoma (CRC). However, methylation in colorectal cancer is still poorly characterized. Method By integration of DNA methylation data from the GEO database and gene expression data from The Cancer Genome Atlas database, the aberrantly methylated genes involved in CRC tumorigenesis were identified. Subsequent in vitro experiments further validated their role in CRC. Results We performed integrative genomic analysis and identified HPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. K-M survival analysis showed that hypermethylation–low expression of heparanase 2 (HPSE2) was related to poor patient prognosis. Overexpression of HPSE2 reduced cell proliferation in vivo and in vitro. HPSE2 could regulate the p53 signaling pathway to block the cell cycle in G1 phase. Conclusion HPSE2, a novel tumor suppressor gene that is frequently inactivated through promoter methylation in CRC. HPSE2 performs a tumor suppressive function by activating the p53/ p21 signaling cascade. The promoter hypermethylation of HPSE2 is a potential therapeutic target in patients with CRC, especially those with late-stage CRC.

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