McGill EMC Release 4 for assay "smRNA-seq": Transcriptome profiling by high-throughput sequencing
A IPS05_X_NPC_mRNA-Seq paired end data for Neural progenitor cells(Nestin)
A KNIH002 mRNA-seq paired end data for islet cells
A IPS03_N_ENeuron_mRNA-Seq paired end data for Early neuron cells(Tuj1)
A IPS06_X_ENeuron_mRNA-Seq paired end data for Early neuron cells(Tuj1)
McGill EMC Release 4 for assay "mRNA-seq": Transcriptome profiling by high-throughput sequencing
Gene expression comparison between human colonic epithelial cells cultured with Klebsiella pneumoniae (KP) derived from PSC patients versus KP JCM1662.
A IPS05_X_NPC_smRNA-Seq single end data for Neural progenitor cells(Nestin)
A IPS06_X_ENeuron_smRNA-Seq single end data for Early neuron cells(Tuj1)
In our previous work, we used a myoblast model of fusion-positive rhabdomyosarcoma (FP-RMS) to demonstrate that FGF8, a target of the PAX3-FOXO1 (P3F) transcription factor, is essential for tumorigenicity driven by P3F. When aberrantly expressed, FGF8 can also sustain tumorigenicity in recurrent tumors that are independent of P3F. In this study, we report that FGF8, along with its receptors FGFR1 and FGFR4, is often highly expressed in FP-RMS tumors. We found that high levels of FGF8 expression in FP-RMS cells correlate with increased sensitivity to an FGFR4 inhibitor and a pan-FGFR inhibitor. Conversely, downregulating FGF8 led to a loss of sensitivity to these inhibitors. Interestingly, when FGF8 was upregulated in myoblasts, it resulted in decreased FGFR4 expression and sensitized the cells to an FGFR1 inhibitor and a pan-FGFR inhibitor. The downregulation of FGFR4 expression mediated by FGF8 could be reversed by inhibiting FGFR1, MEK, or ERK, thereby defining a signaling pathway through which FGF8 exerts its regulatory effects. Additionally, we discovered that high FGF8 expression in P3F-independent recurrent tumors is due to a rearrangement of viral long terminal repeat (LTR) sequences into the 3' untranslated region (UTR) of FGF8, leading to increased stability of FGF8 mRNA. These findings indicate that FGF8 plays an oncogenic role in FP-RMS through FGFR4 and may also exert oncogenic effects in P3F-independent relapses via FGFR1. Our study highlights the functional significance of FGF8 in FP-RMS and supports the rationale for preclinical investigations of FGFR inhibitors in treating this type of cancer.
