Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown.
Researchers from the National University of Malaysia amied to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. The exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. The researchers performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. They validated their microarray data using serum samples. They performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p < 0.05, the researchers identified 105 significantly upregulated and 34 downregulated circRNAs in HCT116-R exosomes. Knockdown of circ_0000338 improved the chemo-resistance of CRC cells. They have proposed that circ_0000338 may have dual regulatory roles in chemo-resistant CRC. Exosomal circ_0000338 could be a potential biomarker for further validation in CRC.
Hierarchical clustering and volcano plot used to identify differentially expressed circRNAs between exosomes. (Fold change >2, p < 0.05).