GSE201905
miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells
Post-transcriptional regulation of genes is heavily dependent on the action of miRNAs. miRNAs take part in various cellular processes and have been shown to be crucial in oncogenesis. Identification of miRNA targets is crucial for understanding its functions in different cellular contexts. miR-148a-3p is highly expressed in HCT116 cells and several other cell lines. However, the studies about mRNA targetting activitiy of this miRNA was limited. In this study, we aimed at identifying target repotoire of miR-148a-3p by using HCT116 DROSHA-KO model. We found several genes that are under miR-148a-3p regulation, including several reported targets. We next found the negative association between miR-148a-3p and DDX6, one of the identified gene, in leukemia. We examined DDX6 functions in this cancer and showed that the depletion of DDX6 helps impair leukemia cell growth, promote apoptosis and increase survival rate of transplanted mice. We then identified that DDX6 functions to suppress TXNIP, a well known tumor suppressor in leukemia and various types of cancer. Our findings uncovered the regulation axis between miR-148a-3p/DDX6/TXNIP in leukemia which provides molecular mechanism basis for therapeutic treatment directions. Overall design: mRNA sequencing and small RNA sequencing