LAUSR

Background: We previously identified SPARC-like 1 (SPARCL1) as a suppressor for colon cancer metastasis. Recent studies confirmed its epigenetic modification in prostate cancer and osteosarcoma. Here we conducted in vivo and in vitro studies to investigate the mechanism of SPARCL1 epigenetic regulation and the relationship with clinicopathological features. Method: Tissue array (271 left- [LCC] and 257 right-sided colon cancer [RCC]) and immunohistochemistry were performed to measure SPARCL1 expression. Methylation status was compared by bisulfite sequencing PCR between 17 LCC and 16 RCC. Epigenetic alteration and rescue experiment were performed in colon cancer cell lines (HCT-116, RKO and HT-29) using decitabine, panobinostat, or siRNA. Transwell assay was employed to compare cell mobility. Chi-square test, Mann-Whitney U test were used for comparing SPARCL1 expression or other clinical characteristics, and t-test for cell motility. Result: RCC significantly lower expressed SPARCL1 protein than LCC (P =0.007). High methylated CpG site of SPARCL1 enriched in RCC not in LCC (56.25% vs. 29.41%). In vitro studies confirmed that decitabine could up regulate SPARCL1 transcription by 72-fold. Transwell assays further revealed that significant inhibition of decitabine in decreasing cells invasion and migration properties, which could be rescued by siRNA against SPARCL1. In addition, we didn9t observe transcriptional alteration with panobinostat treatment. Conclusion: DNA methylation not histone acetylation modulated SPARCL1 expression and suppress tumor metastasis, which may contribute to aberrant expression pattern and different clinical outcomes varying in left and right-colon cancer. Citation Format: Dehao Wu, Wen Cai, Junxi Xu, Xue Liu, Rui Bai, Shu Zheng, Weiting Ge, Hanguang Hu. SPARCL1 exhibits different expression pattern between left- and right- sided colon cancer and it was down-regulated via DNA methylation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1277.