GSE196405
Oncofetal protein IGF2BP1 regulates IQGAP3 expression to maintain stem cell potential in cancer [RNA-Seq]
We reported earlier that IQGAP3 is an important stem cell factor in rapidly proliferating  isthmus stem cells in the stomach. Furthermore, we observed robust induction of  IQGAP3 expression in terminally differentiated chief cells and de-differentiated cells  following tissue damage. The elevated expression of IQGAP3 in cancer and its  association with metastasis suggest a fundamental role for IQGAP3 in proliferating  cancer stem cells. What causes the upregulation of IQGAP3 in cancer is unclear. Here,  we show that IGF2BP1 and IQGAP3 expression levels are highest in the blastocyst,  with both showing decreases during adulthood. This suggests that IQGAP3, like  IGF2BP1, is an early developmental gene that is aberrantly upregulated upon reexpression  of IGF2BP1 during carcinogenesis. We found that IGF2BP1 binds and  stabilizes m 6 A-modified IQGAP3 transcripts. Furthermore, downstream targets of  IGF2BP1, namely SRF and FOXM1, also upregulate IQGAP3 expression. These  multiple layers of IQGAP3 regulation, which may safeguard against inappropriate stem  cell proliferation, present additional drug targets to inhibit IQGAP3-driven malignant growth. Overall design: RNA expression profile of NTERA2 cells treated with sicontrol, siSRF, siIGF2BP1, siFOXM1 and siIQGAP3 for 7 days. Total RNA from the cell pellets was extracted using RNeasy Kit (Qiagen) with the removal of genomic DNA using the RNase-free DNase Set (Qiagen) according to the manufacturer's instructions. RNA samples were sent to Beijing Genomics Institute (BGI) for cDNA synthesis, PCR amplification, transcriptome library preparation and sequencing.Triplicate samples are shown.