CHST11 gene expression and DNA methylation in breast cancer

Abstract

Our previously published data link P-selectin-reactive chondroitin sulfate structures on the surface of breast cancer cells to metastatic behavior of cells. We have shown that a particular sulfation pattern mediated by the expression of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness of human breast cancer cell lines. The present study was performed to evaluate the prognostic value of CHST11 expression and determine whether aberrant DNA methylation controls CHST11 expression in breast cancer. Publicly available datasets were used to examine the association of CHST11 expression to aggressiveness and progression of breast cancer. Methylation status was analyzed using bisulfite genomic sequencing. 5-aza-2′-deoxycytidine (5AzadC) was used for DNA demethylation. Reduced representation bisulfite sequencing was performed in the CpG island of CHST11 with a minimum coverage of 10. Quantitative real-time RT-PCR was employed to confirm the expression profile of CHST11 in breast cancer cell lines. Flow cytometry was also used to confirm the expression of the CHST11 product, chondroitin sulfate A (CS-A). The expression of CHST11 was significantly higher in basal-like and Her2-amplified cell lines compared to luminal cell lines. CHST11 was also highly expressed in cancer tissues compared to normal tissues and the expression levels were significantly associated with tumor progression. We observed very low levels of DNA methylation in a CpG island of CHST11 in basal-like cells but very high levels in the same region in luminal cells. Treatment of MCF7 cells, a luminal cell line with very low expression of CHST11, with 5AzadC increased the expression of CHST11 and its immediate product, CS-A, in a dose-dependent manner. These results suggest that CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the methylation status of this gene also has potential as a prognostic biomarker.

Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of GCM2, ITPRIPL1 and CCDC181 for Detection of Early Breast Cancer and Surgical Treatment Response

“…In total, 160 highly methylated genes were found when the genes identified from the Taiwanese and TCGA cohorts were combined ( Table S2 ). A literature review was conducted and the following previously-reported aberrantly methylated genes were excluded: DPF1 [ 36 ], DNM3 [ 16 ], TLX1 [ 37 ], CHST11 [ 38 ], CHST3 [ 39 ], ALX1 [ 40 ], HNF1B [ 37 ], EBF1 [ 41 ], PITX2 [ 42 ], ITGA5 [ 43 ], COL11A2 [ 44 ], CFTR [ 45 ], NR5A2 [ 46 ], PRKCB [ 46 ], SOSTDC1 [ 47 ], DBX1 [ 48 ], LHX8 [ 49 ], HCK [ 50 ], NXPH1 [ 51 ], NID2 [ 52 ], TAC1 [ 53 ], TFAP2B [ 54 ], F2RL3 [ 55 ], POU4F2 [ 56 ], H2AFY [ 57 ], GALR1 [ 58 ], FOXD3 [ 59 ], NT5E [ 60 ], CLIP4 [ 61 ], ZNF454 [ 62 ], TIMP2 [ 63 ], GNG4 [ 64 ], MIR129-2 [ 64 ], TXNRD1 [ 65 ], CPXM1 [ 64 ], PRDM14 [ 64 ], HOXA4 [ 66 ], SLITRK1 [ 67 ], AHRR [ 68 ], NPTX2 [ <...>…”

Reduction of pl-CSA through ChSy-2 knockout inhibits tumorigenesis and metastasis of choriocarcinoma in JEG3 cells

“…However, the enzymes involved in pl-CSA synthesis are unclear. Existing researches have confirmed that ChSy-2 has a higher glycosyltransferase activity for CSA than for other CSs and is also highly expressed in placental 17 and cancerous tissues 18 ; thus, it is involved in CSA production 29 , 30 . According to the above thesis, we speculated that ChSy-2 may be the key synthase for pl-CSA production.…”

Identification of Tumor Microenvironment-related Prognostic Genes in Colorectal Cancer based on Bioinformatic Methods

“…According to research findings, the expression level of CHST11 is significantly correlated with the progression of a variety of tumors 41,42 . Studies have shown that CHST11 is a new gene that can effectively detect CRC in cell-free DNA 43 .…”