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

被引:6
作者
Hu, Hanguang [1 ,2 ]
Wu, Dehao [1 ]
Liu, Xibo [3 ]
Yu, Haifeng [2 ,4 ,5 ]
Xu, Junxi [6 ]
Cai, Wen [1 ,6 ]
Huang, Yanqin [1 ]
Bai, Rui [1 ]
Zhang, Jiawei [1 ]
Gu, Ying [7 ]
Zheng, Shu [1 ]
Ge, Weiting [1 ,8 ]
机构
[1] Zhejiang Univ, Key Lab Mol Biol Med Sci, Key Lab Canc Prevent & Intervent,Affiliated Hosp, Canc Inst,China Natl Minist Educ,Sch Med, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Oncol, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[3] Shaoxing Peoples Hosp, Dept Pathol, 568 Zhongxing North Rd, Shaoxing 312000, Zhejiang, Peoples R China
[4] Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Lymphat Med Oncol, Hangzhou 310005, Zhejiang, Peoples R China
[5] Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou, Zhejiang, Peoples R China
[6] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Gastroenterol, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China
[7] Zhejiang Univ, Inst Genet, Zijingang Campus,Yuhangtang Rd 388, Hangzhou 310058, Zhejiang, Peoples R China
[8] Zhejiang Univ, Canc Ctr, Hangzhou 310000, Zhejiang, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
DNA methylation; left-sided colon cancer; metastasis; right-sided colon cancer; SPARCL1; COLORECTAL-CANCER; DISTAL; HEVIN; SPARC-LIKE-1; PHENOTYPE; PROFILES;
D O I
10.2217/epi-2021-0231
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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-sided 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. 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.
引用
收藏
页码:1269 / +
页数:14
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