Methylation-mediated expression of SPARC is correlated with tumor progression and poor prognosis of breast cancer

Abstract

Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The study aims to investigate the status of DNA methylation and the biofunction of SPARC in breast cancer. The qRT-PCR, BGS, and MSP methods were respectively employed to measure the relative mRNA expression levels and methylation status of SPARC. Additionally, the effects of SPARC on cell proliferation, migration, and invasion were examined in SPARC overexpression and knockdown cells. Immunohistochemical staining and western blot assay were used to examine the protein expression of genes. The expression levels of SPARC were found to be higher in breast cancer tissues and most breast cancer cells. The expression levels of SPARC in MDA-MB-231 and MCF-7 cells were significantly reversed by 5-Aza-dC treatment. Furthermore, the high expression and promoter DNA hypomethylation of SPARC were detected in triple-negative breast cancer tissues, while no expression changes of SPARC were found in luminal A breast cancer tissues. Overexpression of SPARC dramatically promoted MCF-7 cells migration and invasion, while knockdown of SPARC inhibited MDA-MB-231 cells migration and invasion. SPARC was involved in the epithelial-mesenchymal transition (EMT) process of breast cancer cells. The expression levels of mesenchymal markers N-cadherin, Vimentin, and β-catenin were upregulated, while E-cadherin was downregulated in SPARC overexpressed breast cancer cells. Conversely, the expression levels of EMT-related genes demonstrated the opposite trend in SPARC knockdown cells. To conclude, high expression of SPARC regulated by promoter hypomethylation promotes breast cancer cells migration and invasion, thus SPARC may act as an oncogene and serve as a potential target for breast cancer therapy.

The Matricellular Protein SPARC Decreases in the Lacrimal Gland At Adulthood and During Inflammation

“…This has been the case in breast cancer, where high expression of SPARC induced by promoter hypomethylation has been shown to promote cell migration and invasion. 37 Of interest to our study are previous findings showing hypermethylation of the Sparc gene promoter and decreased synthesis of SPARC in aging mice, which has been linked to degeneration of the intervertebral discs and chronic low back pain. 19 Our results showing increased overall methylation levels in the adult lacrimal gland are in line with these findings and identified Sparc gene hypermethylation at three out of four CpG sites analyzed.…”

Omics Overview of the SPARC Gene in Mesothelioma

“…Methylation-mediated SPARC expression was shown to correlate with tumor progression and poor prognosis of breast cancer. Overexpression of SPARC may promote cancer cell migration and invasion, and thus function as an oncogene and a potential therapeutic target for breast cancer [30]. The relationship between stromal-cell-derived SPARC and its clinicopathologic significance was reported in human gastric cancer tissue [31].…”