To development of targeting therapy against cancer stem-like cells (CSLCs), we examined therapy resistance of CSLCs and identified a responsible gene for the CSLC phenotype. Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique medium. To assess the chemoresistance and liver metastasis, MTS assay and splenic injection were performed. Expressional analyses were performed using RNA-seq, qPCR, flow-cytometry, and ELISA.
The obtained CSLCs showed increased chemoresistance and metastatic potentials. A RAB3B was identified as an up-regulated gene in both CSLCs and poor prognostic HCCs by RNA-seq. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, cell cycle, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion in CSLCs were not observed in the RAB3B-KO cells.
It was suggested that the up-regulation of RAB3B plays important roles in CSLCs.