Abstract
Colorectal cancer (CRC) ranks as the most common gastrointestinal solid carcinoma globally. Substantial evidence has established a pivotal role for circular RNAs (circRNAs) in CRC progression. In this study, differentially expressed circRNAs were analyzed based on a public dataset (GSE126094) and elevated expression of circCASK (hsa_circ_0001917) was validated in CRC. Moreover, increased circCASK was also confirmed in CRC patients. Functionally, circCASK knockdown led to a significant decrease in CRC cell growth and attenuated cell migration and invasion. Similarly, circCASK knockdown markedly attenuated tumor growth in vivo. Mechanistically, circCASK sponged miR-1271-5p and enhanced sine oculis homeobox homolog 1 (SIX1) expression. More importantly, both SIX1 overexpression and miR-1271-5p knockdown could reverse the cellular behavior inhibition induced by circCASK knockdown. Furthermore, SIX1 was most strongly and positively linked with Wnt/β-catenin signaling pathways, circCASK triggered Wnt/β-catenin signaling through the miR-1271-5p/SIX1 axis, and FOXC2 transcriptionally induced circCASK expression. In conclusion, circCASK induced by FOXC2 accelerated CRC progression through the miR-1271-5p/SIX1 axis, thus providing an interesting insight into CRC tumorigenesis.
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