Mapping a Circular RNA-microRNA-mRNA-Signaling Regulatory Axis That Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells.

摘要: Spheroidal cancer cell cultures have been used to enrich stem cells (CSC), which are thought contribute important clinical features of tumors. This study aimed map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal (CRC) spheroid cells. The established from two CRC lines acquired stemness properties pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 636 circRNAs specific parental cells, respectively. In spheroids, algorithmic analyses unveiled a core network mRNAs involved modulating stemness-associated signaling pathways, circRNA-microRNA (miRNA)-mRNA axis. major circRNAs, hsa_circ_0066631 hsa_circ_0082096, this were significantly up-regulated levels predicted target experimentally shown down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p miR-579, confirming circRNA sponging targeted miRNAs. Furthermore, affected miRNAs demonstrated inhibit degradation six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 WNT5, These encode proteins that reported variously regulate GP130/Stat, Activin/Nodal, TGF-β/SMAD or Wnt/β-catenin pathways controlling various aspects CSC stemness. Using model, novel circRNA-miRNA-mRNA axis mapped work forms foundation for elucidation molecular mechanisms complex cellular biochemical processes determine possibly designing therapeutic strategies treatment targeting CSC.