SPARCL1 exhibits different expressions in left- and right-sided colon cancer and is downregulated via DNA methylation

Hanguang Hu1,2, Dehao Wu1, Xibo Liu3

  • 1Cancer Institute, Key Laboratory of Cancer Prevention & Intervention, China National Ministry of Education; Key Laboratory of Molecular Biology in Medical Sciences; the Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China.

Epigenomics
|August 26, 2021
PubMed

Insights

SPARCL1 gene methylation suppresses colorectal cancer metastasis. Higher SPARCL1 expression in left-sided colon cancer suggests prognostic value.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • SPARCL1 (SPARCL1) was previously identified as a suppressor of colorectal cancer (CRC) metastasis.
  • Understanding the epigenetic regulation of SPARCL1 is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the epigenetic mechanism regulating SPARCL1 expression in colon cancer.
  • To explore the relationship between SPARCL1 expression, DNA methylation, and clinicopathological features, particularly in left-sided colon cancer.

Main Methods:

  • Immunohistochemistry used to assess SPARCL1 expression in 528 colon cancer tissue samples (271 left-sided, 257 right-sided).
  • In vivo and in vitro DNA methylation states analyzed using biochemical sulfide potential assay.
  • Cellular models manipulated with siRNA or decitabine to alter SPARCL1 transcription and DNA methylation.
  • Transwell assays employed to compare cellular motility properties.

Main Results:

  • SPARCL1 expression is epigenetically regulated by DNA methylation.
  • DNA methylation-mediated SPARCL1 activity appears to inhibit colorectal carcinoma cell motility.
  • SPARCL1 expression is significantly higher in left-sided colon cancer compared to right-sided.
  • Elevated SPARCL1 expression in left-sided colon cancer may hold prognostic significance.

Conclusions:

  • Epigenetic silencing of SPARCL1 via DNA methylation contributes to colorectal cancer metastasis.
  • SPARCL1 represents a potential therapeutic target for inhibiting colon cancer cell motility.
  • The distinct expression pattern and prognostic value of SPARCL1 in left-sided colon cancer warrant further investigation.