mRNA/sRNA Co-Sequencing Reveals Multiple New Targeted Therapy Candidates in Rhabdomyosarcoma

There have been few studies investigating the transcriptional-driver landscape of rhabdomyosarcoma (RMS). In this study, we performed genome-wide mRNA and sRNA co-sequencing from the same RMS and wildtype tissues to identify differentially expressed and differentially regulated genes involved in the molecular pathology of RMS. One key finding is the upregulation of RUNX2 transcription factor, which is normally under the negative control of HDAC4 transcriptional silencer, but this is lost in these tissues. Similar to bone sarcomas, we propose that HDAC4 itself was under the negative regulated of miR-140, i.e., upregulation of miR-140 silences HDAC4, allowing for the expression of RUNX2. The data showed that most miRNAs known to target HDAC4 (e.g. miR-1, miR-206) including miR-140 were downregulated, with the exception of miR-155. There might be the possibility that miR-140/HDAC4/RUNX2 signalling pathway is specific to bone sarcoma but here, the miR-155/HDAC4/RUNX2 signalling pathway is specific to muscle sarcomas. Further studies are required to test this hypothesis. Overall design: In total, 26 human biopsy samples; 5 Alveolar RMS (ARMS), 4 Embryonal RMS (ERMS), 3 Spindle Cell/Scelorising RMS, 1 Pleomorphic RMS and 13 control skeletal muscle samples. Total RNA was extracted and then mRNA-seq and sRNA-seq were carried out. This contains the mRNA-seq data, while the sRNA-seq data, which includes some of the RMS/control samples is provided separately. Some samples (R09, R11, R12, R13, R14, R17, R18, R21, R22, R24, R25, R26) were resequenced due to quality of the samples.