circSKA3 promotes colorectal cancer metastases through miR-1238 and methylation

Abstract

Colorectal cancer (CRC) is becoming one of the most common cancers overworld, which causes a high rate of death in patients. circRNAs are non-coding RNAs(ncRNAs), which have been reported to be involved in the development of many cancers, including CRC. However, the exact mechanism that how circRNAs function through in CRC remains unclear. In this study, we firstly used GEO database and bioinformatic methods to identify the significant changed circRNAs, with circSKA3 being the most significantly upregulated circRNAs in CRC tissues. PCR results further confirmed higher expression of circSKA3 in CRC patients. CCK-8, scratch, and transwell assays indicated that circSKA3 could promote the proliferation, migration, and invasion of CRC cell lines for cell detection. Dual-luciferase assays were carried out to detect the downstream targets of circSKA3, and a binding site between circSKA3 and miR-1238 was identified and miR-1238 could also combine with YTHDF2. Overexpression of YTHDF2 rescued the decreased cell proliferation, migration, and invasion caused by miR-1238 overexpression. RIP assay further indicated that YTHDF2 could decrease the methylation of STAT5A. In summary, our study found that circSKA3 was upregulated in CRC tissues comparing with normal tissues. circSKA3 could increase the expression ofYTHDF2 through sponging miR-1238 to decrease the methylation of STAT5A, which could provide a novel target for CRC treatment.