https://orcid.org/0000-0002-4769-0251
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Abstract
Aim: The authors previously found that SPARCL1 functions to suppress colorectal cancer metastasis. Here, the epigenetic mechanism of SPARCL1 regulation and its relationship with clinicopathological features in colon cancer were investigated. Materials & methods: SPARCL1 expression was evaluated by immunohistochemistry staining in a tissue array containing 271 left-sided colon cancer samples and 257 right-sided colon cancer samples. In vivo and in vitro DNA methylation states were measured by biochemical sulfide potential assay. The transcription and DNA methylation states in cells were altered by siRNA or decitabine treatment, respectively. Cellular motility properties were compared through transwell assay. Results & conclusion: SPARCL1, mediated by its DNA methylation, may arrest colorectal carcinoma motility. Furthermore, SPARCL1 expression is higher and may have a specific prognostic value in left-sided colon cancer.
Lay abstract
The heterogeneity of colorectal cancer is largely based on their primary tumor locations. For example, patients with left-sided colon cancer generally have better prognoses and different treatment strategies in comparison with patients with right-sided colon cancer. Research is required to uncover the mechanisms underlying these differences. The authors showed that the addition of methyl groups (DNA methylation) to DNA encoding SPARCL1 (a protein involved in cell adhesion) could inhibit regular colorectal cell motility. Furthermore, SPARCL1 protein expression was higher and positively correlated with better prognosis specifically in patients with left-sided colon cancer. The present study provides an evidential basis for the different molecular biological features between left- and right-sided colon cancer. SPARCL1 is a promising candidate for predicting colon cancer prognosis and potential therapeutic intervention. Further in-depth study of SPARCL1 would be of great value for clinical application.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0231
Financial & competing interests disclosure
This study was supported by the National Key R & D Program of China (no. 2016YFC1302803), the Fundamental Research Funds for the Central Universities (no. K20200068), the National Key R & D Program of China (no. 2018YFA0800100 and 2018YFA0800102), the National Natural Science Foundation of China (no. 31970555) and the Basic Public Welfare Research Project of Zhejiang Province (no. LQ19H160024). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval by the Institutional Review Board (IRB) of the Second Affiliated Hospital of Zhejiang University under protocol 2019-252. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
Availability of data & materials
All data generated or analyzed during this study are included in this published article.