CCDC26 knockdown enhances resistance of gastrointestinal stromal tumor cells to imatinib by interacting with c-KIT.

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are involved in diseases such as cancer. However, little is known about the role of lncRNAs in gastrointestinal stromal tumors (GIST). In the present study, we explored the biological function of the lncRNA coiled-coil domain-containing 26 (CCDC26) in imatinib resistance of GIST. We found that human GIST-882 cells with lower CCDC26 expression were less sensitive to imatinib compared with GIST-T1 cells with higher CCDC26 expression. CCDC26 expression decreased in a time-dependent manner in the presence of imatinib. Moreover, small interfering RNA (siRNA) knockdown of CCDC26 increased GIST cell sensitivity to imatinib. The RNA pull-down experiment showed that CCDC26 can interact with c-KIT and that CCDC26 knockdown can upregulate c-KIT expression. We also found that inhibiting c-KIT induced resistance to imatinib. Lastly, we proved that inhibiting c-KIT can reverse CCDC26 knockdown-mediated imatinib resistance in GIST. We suggest that CCDC26 knockdown can induce imatinib resistance in GIST cells by downregulating c-KIT expression. Our results provide a novel insight into imatinib resistance in GIST.