Morin Promotes Cell Apoptosis By Suppressing Lxrα Expression and Transcription Activity in Imatinib-Resistant Chronic Myeloid Leukemia Cell

The abnormal activation of alternative signaling pathways plays an important role in Imatinib (IM) resistance chronic myeloid leukemia (CML). Therefore, there is an urgent need to determine the mechanism underlying IM resistance induced by abnormal signaling pathway activation and develop alternative treatment strategies. Here, we found that miR-188-5p expression was significantly upregulated while the protein level of PTEN was downregulated in IM-resistant CML cells. Notably, Morin could promote cell apoptosis and increase IM sensitivity by regulating the miR-188-5p/PTEN pathway. Furthermore, we found the overexpression of LXRα in IM-resistant CML cell. Knockdown of LXRα attenuated apoptosis in IM-resistant CML cells. Mechanistically, we revealed that LXRα bound to the parent gene of miR-188-5p promoter and positively regulated miR-188-5p expression at transcriptional level. Morin not only decreased LXRα expression but also reduced the transcriptional activation of LXRα in IM-resistant CML cells, thus blocking the miR-188-5p/PTEN axis. In conclusion, our findings provide the evidence that Morin can be used as a novel therapeutic approach for treating of IM-resistant CML by regulating the LXRα/miR-188-5p/PTEN pathway.

No relevant conflicts of interest to declare.