Secreted frizzled-related protein 1 (SFRP1) is a gene that belongs to the secreted glycoprotein SFRP family. SFRP1 has been classified as a tumor suppressor gene due to the loss of expression in various human cancers, which is mainly attributed by epigenetic inactivation via DNA methylation or transcriptional silencing by microRNAs. Epigenetic silencing of SFRP1 may cause dysregulation of cell proliferation, migration, and invasion, which lead to cancer cells formation, disease progression, poor prognosis, and treatment resistance. Hence, restoration of SFRP1 expression via demethylating drugs or over-expression experiments opens the possibility for new cancer therapy approach. While the role of SFRP1 as a tumor suppressor gene is well-established, some studies also reported the possible oncogenic properties of SFRP1 in cancers. In this review, we discussed in great detail the dual roles of SFRP1 in cancers—as tumor suppressor and tumor promoter. The epigenetic regulation of SFRP1 expression will also be underscored with additional emphasis on the potentials of SFRP1 in modulating responses toward chemotherapeutic and epigenetic-modifying drugs, which may encourage the development of novel drugs for cancer treatment. We also present findings from clinical trials and patents involving SFRP1 to illustrate its clinical utility, extensiveness of each research area, and progression toward commercialization. Lastly, this review provides directions for future research to advance SFRP1 as a promising cancer biomarker.
The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using the Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. The majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes.
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite significant advances in the diagnostic services and patient care, several gaps remain to be addressed, from early detection, to identifying prognostic variables, effective treatment for the metastatic disease, and the implementation of tailored treatment strategies. MicroRNAs, the short non-coding RNA species, are deregulated in CRC and play a significant role in the occurrence and progression. Nevertheless, microRNA research has historically been based on expression levels to determine its biological significance. The exact mechanism underpinning microRNA deregulation in cancer has yet to be elucidated, but several studies have demonstrated that epigenetic mechanisms play important roles in the regulation of microRNA expression, particularly DNA methylation. However, the methylation profiles of microRNAs remain unknown in CRC patients. Methylation is the next major paradigm shift in cancer detection since large-scale epigenetic alterations are potentially better in identifying and classifying cancers at an earlier stage than somatic mutations. This review aims to provide insight into the current state of understanding of microRNA methylation in CRC. The new knowledge from this study can be utilized for personalized health diagnostics, disease prediction, and monitoring of treatment.