Table 1 Altered mRNA expression important for tumor cell invasion

From: Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion

Gene	Gene function	V vs PF	V vs P3
mRNA that promote tumor invasion
Capn6	Cytoskeletal organization	33.45
Cdh6	Type II cadherin, development	23.23	9.17
^a Adamts1	Metalloprotease	21.98	5.65
Msln	Cell adhesion; overexpressed in cancers	20.93	48.60
^a Adamts5	Peptidase; aggrecanase to cleave aggrecan	7.68
^a, ^b Cnr1	G-protein signaling	6.92
Hoxb9	Transcriptional activator increased in cancers	6.34
^a, ^b, ^c Fgfr4	FGF receptor	6.12
^a, ^b Igf2	Growth factor	5.37	−13.18
^c Plxna2	Semaphorin co-receptors	3.32
Erbb3	EGFR receptor tyrosine kinases	3.10	−4.04
Klf5	Possible transcription factor	2.84
Pbx3	Transcriptional activator	2.59
Stat3	Expression of genes in response to cell stimuli	2.58
^c Sulf2	Remove 6-O-sulfate groups from heparan sulfate	2.52
^c Lamc1	Mediate attachment, migration-interacting extracellular matrix	2.45
Pkp2	Linking cadherins to intermediate filaments	2.40
Cdc25b	Activates the cyclin-dependent kinase CDC2	2.20
^a Ncam1	Cell adhesion; cell-to-cell interactions	2.00	−2.95
Tpm3	Provide stability to actin filaments	−2.08
Fscn1	Cell migration, motility and adhesion	−2.09
Mdm2	E3 ubiquitin-protein ligase	−2.12
^a Adam19	Matrix metalloproteinase	−2.15	−3.08
^a Jag2	Ligand that activates Notch	−2.17	−4.05
Cttn	Adherins and cytoskeleton	−2.23
Arpc5	Control of actin polymerization	−2.34
^a, ^c Abi1	Mediates signal transduction from Ras to Rac	−2.42
^a Jak1	Cell signal transduction	−2.45
Mmp14	Metalloproteinase	−2.58
Ifitm1	Implicated in cell adhesion	−2.68	−2.88
^a Elk3	Activated by signal-induced phosphorylation	−2.74
Vim	Cytoskeletal protein	−2.90
Id1	Inhibits the DNA-binding transcription factors	−3.00
Pak1	Cell motility and morphology	−3.21
^a Cyr61	Promotes the adhesion of endothelial cells	−3.28
^a Dusp1	Cellular response to environmental stress	−3.62
^a Lasp1	Binds to the actin cytoskeleton	−3.91
Ntn4	Protein related to laminins	−4.93
Etv4	Transcriptional activator	−5.12
^a, ^c Flnb	Filamin; repair vascular injuries	−5.82
Axl	Transduces signals from the extracellular matrix	−6.04
^a Igfbp2	Inhibits IGF-mediated growth	−8.64
Cxcl12	Chemotaxis; embryonic development	−19.80	−14.90
^b Ahr	Ligand-activated transcriptional activator		11.13
Egfr	Receptor for members of EGF family		4.82
Eps8	Functions as part of the EGFR pathway		3.59
Sema3e	Axon guidance; Semaphorins		3.43
Galnt2	Oligosaccharide biosynthesis		2.64
Sparc	Involved in ECM synthesis		2.44
Ghr	Transmembrane receptor for growth hormone		2.28
Prdx1	Antioxidant protective		2.27
Emp3	Involved in proliferation and cell–cell interactions		2.04
Rnf11	Transcriptional activator		−2.01
Myo5a	Cytoplasmic vesicle transport and anchorage		−2.09
^b, ^c Igf1r	Critical role in transformation events		−2.13
Hes6	Promotes cell differentiation		−2.17
Abl2	Non-receptor tyrosine protein kinases		−2.21
Peak1	Role in cell spreading and migration		−2.24
Zkscan3	Transcriptional regulator		−2.35
Tppp3	Tubulin and has microtubule-bundling activity		−2.45
St3gal1	Transfer of sialic acid to substrates		−2.47
Bach1	Transcription factor		−2.50
^b Epha2	Ephrin receptor subfamily		−2.53
Notch1	Developmental processes by controlling cell fate		−3.07
Jun	Transcriptional activator		−3.12
Kdm5b	Histone demethylase; transcriptional corepressor		−3.17
^c Sema6a	Cell surface receptor for cell–cell signaling		−3.46
^b, ^c Met	Hepatocyte growth factor receptor		−3.73
Nuak1	Multifunctional kinase		−3.87
Serpine2	Inhibit serine proteases		−4.99
mRNA that inhibit tumor invasion
^a, ^b Igfbp5	Alter the interaction of IGFs with receptor	8.28	−5.68
^c Spry1	Antagonist of FGF pathways	7.39
Serpinb1	Proteinase inhibitor	6.48
^a Dcx	Bind microtubules	5.16
Col4a2	Inhibitor of angiogenesis and tumor growth	2.83
Cd82	Metastasis suppressor	2.62	−2.37
Spry2	Inhibitory effect on growth factor signaling	−2.10
Deptor	Negative regulator of the mTORC1 signaling	−2.12
^c Cited2	Inhibits transactivation of HIF1A-induced genes	−2.26	−4.02
Actn1	Nonmuscle, cytoskeletal, alpha actinin isoform	−2.32
Flna	Remodeling the cytoskeleton	−2.43
Lpp	Involved in cell–cell adhesion and cell motility	−2.62
^c Dlg5	Transmission of signals to the cytoskeleton	−2.66
^a Timp2	Inhibitors of the matrix metalloproteinases	−2.68
Tagln	Actin crosslinking/gelling protein	−2.70	−3.56
^c App	Transcriptional activator	−2.88
Cdk1	Cell cycle regulatory kinase	−3.01
Creb3l1	Transcriptional activator	−3.04
Dusp4	Phosphatase; negatively regulate (MAP) kinases	−3.08
^a Id3	Inhibits the DNA-binding transcription factors	−3.13
Wisp1	Downstream in the WNT1 signaling pathway	−3.32	−2.36
Rgs16	Inhibits signal transduction	−3.78	−4.93
^c Tns3	Cell migration and bone development	−4.18	−4.30
Filip1l	Regulator of the anti-angiogenic activity	−5.68	−2.21
Sox4	Regulation of embryonic development	−6.48	−2.91
^a Akap12	Scaffold protein in signal transduction	−7.98	−3.87
Fstl1	Modulate action of growth factors	−8.56	−2.16
^c Mme	Metallopeptidase		15.17
^c Gprc5a	Development, cellular growth and differentiation		3.67
Nefl	Intracellular transport to axons and dendrites		3.31
Dusp6	Negatively regulate (MAP) kinases		2.93
Galnt7	GalNAc transferase 7		2.48
Adam9	Biological processes: cell–cell/matrix interactions		2.44
Flnc	Crosslink actin filaments		−2.15
Rhob	Cell adhesion and growth factor signaling		−2.58
Mtss1	Actin bundling		−2.77
Igfbp3	Bind and inhibit IGF (affect growth)		−3.33
^c Dyrk2	Cellular growth and/or development		−3.36

Abbreviations: FGF, fibroblast growth factors; EGFR, epidermal growth factor receptor; IGF, insulin-like growth factor.
Total RNA was isolated using the miRNeasy mini kit (Qiagen), allowing for the isolation of RNA <30 bp in length, according to the manufacturer’s specifications. Poly-A+ mRNA was isolated from 4 μg total RNA, to generate the cDNA libraries, using the Illumina sample preparation kit according to the manufacturer’s specifications (Illumina, San Diego, CA, USA). The cDNA libraries were provided a unique index identifier, allowing the clustering of several samples into a single sequencing lane, and deep-sequencing analyses were performed in triplicate from three independent cell growth, RNA isolation and cDNA library constructions. The raw data were groomed and trimmed for quality of the read using online Galaxy analysis (https://usegalaxy.org), resulting in 40–41 high-quality base pair reads for each sequence with between 4–6 million independent reads for each sample. The sequences were mapped to the mouse genome using Tophat analysis, transcripts were assembled using the Cufflinks program, and individual replicates were merged into a single file using Cuffmerge. The resulting transcript reads were normalized using Fragments Per Kilobase of transcript per Million mapped reads analysis, which normalizes each identified sequence for the length of the identified transcript and the volume of the total read yield from each run. Differential expression was determined from these normalized values comparing vector versus Pax3-FOXO1 (V vs PF) or vector versus Pax3 (V vs P3) using the Cuffdiff program, which not only compares differential expression of the merged files between sets but also utilizes the sequence results from the three independent determinations within each set to assign statistical significance to the differential expression.
^aIndicates genes with similar trends in expression changes in human tumor samples.^{22, 23, 24, 25}
^bIndicates genes demonstrated in the literature to be direct targets of PAX3 or PAX3-FOXO1.^{15, 16, 20, 21}
^cIndicates genes with known PAX3-FOXO1 binding sites in their promoter.²⁰

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Table 1 Altered mRNA expression important for tumor cell invasion

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