<p>Table S1. Sequencing data of SW480/STAT3-siRNA and SW480/siRNA-control.</p><p>SW480/STAT3-siRNA SW480/siRNA-control Type Counts Percentage (%) Counts Percentage (%) high quality reads 14,462,458 100% 10,938,240 100% 3'adaptor-null 10,019 0.07% 7,666 0.07% insert-null 7,589 0.05% 8,732 0.08% 5'adaptor-contaminants 92,858 0.64% 113,141 1.03% sadaptor-contaminantsmaller than 18nt  269,571 1.86% 219,626 2.01% polyA 1,018 0.01% 835 0.01% clean reads 14,081,403 97.37% 10,588,240 96.80% Meaning of rows with  in the above table: 3' adaptor-null: number of reads with no 3' adaptor; insert-null: number of reads with no insertion; 5' adaptor-contaminants: number of 5' contaminants; smaller than 18nt: number of reads smaller than 18 nt; polyA: number of reads with polyA; clean reads: number of clean reads after adaptors and contaminants are removed. Table S2. Gene Ontology enrichment analysis of predicted targets of differentially expressed novel miRNAs.</p><p>GO ID GO term Bonferroni Correction GO:0022008 neurogenesis 8.92E-09 GO:0048468 cell development 1.28E-08 GO:0006366 transcription from RNA polymerase II promoter 1.80E-08 GO:0006357 regulation of transcription from RNA polymerase II 2.78E-08 GO:0048699 generation of neurons 5.47E-08 GO:0048856 anatomical structure development 7.96E-08 GO:0048731 system development 1.13E-07 GO:0007399 nervous system development 1.13E-07 GO:0048869 cellular developmental process 4.83E-07 GO:0007275 multicellular organismal development 4.98E-07 GO:0032502 developmental process 1.28E-06 GO:0019222 regulation of metabolic process 1.32E-06 GO:0030030 cell projection organization 1.73E-06 GO:0030182 neuron differentiation 3.84E-06 GO:0019219 regulation of nucleobase, nucleoside, nucleotide and 3.97E-06 nucleic acid metabolic process</p><p>GO:0080090 regulation of primary metabolic process 4.63E-06 GO:0080090 regulation of primary metabolic process 4.63E-06 GO:0030154 cell differentiation 5.19E-06 GO:0051171 regulation of nitrogen compound metabolic process 5.79E-06 GO:0009889 regulation of biosynthetic process 7.11E-06 GO:0031326 regulation of cellular biosynthetic process 9.59E-06 GO:0031323 regulation of cellular metabolic process 1.18E-05 GO:0048513 organ development 9.95E-05 GO:0065007 biological regulation 1.00E-04 GO:0048666 neuron development 1.20E-04 GO:0009888 tissue development 1.70E-04 GO:0016043 cellular component organization 2.60E-04 GO:0051252 regulation of RNA metabolic process 3.20E-04 GO:0060255 ®ulation of macromolecule metabolic process 3.30E-04 GO:0009653 anatomical structure morphogenesis 5.20E-04 GO:0031175 neuron projection development 5.50E-04 GO:0006355 regulation of transcription, DNA-dependent 6.20E-04 GO:0007417 central nervous system development 6.20E-04 GO:0010556 regulation of macromolecule biosynthetic process 6.40E-04 GO:0045449 regulation of transcription 7.40E-04 GO:0010556 regulation of macromolecule biosynthetic process 9.20E-04 GO:0050789 regulation of biological process 9.40E-04 GO:0010468 regulation of gene expression 1.13E-03 GO:0060255 regulation of macromolecule metabolic process 1.13E-03 GO:0065008 regulation of biological quality 3.16E-03 GO:0009987 cellular process 3.49E-03 Table S3. The KEGG analysis of predicted targets mediated by novel miRNAs.</p><p>Term Pathway Gene Percentage Bonferroni correction count (%) hsa04012 ErbB signaling pathway 288 1.32 2.17E-02 hsa04010 MAPK signaling pathway 736 3.36 2.17E-02 hsa04330 Notch signaling pathway 120 0.55 2.63E-02 hsa05212 Pancreatic cancer 179 0.82 2.88E-02 hsa00514 Other types of O-glycan biosynthesis 109 0.50 3.83E-02 Figure S1. Size distributions of small RNAs in SW480/siRNA-control and</p><p>SW480/STAT3-siRNA cells. 22-nucleotide small RNAs are enriched in both samples, which is in line with the typical size of miRNAs. Figure S2. Base compositions of small RNAs in SW480/siRNA-control and</p><p>SW480/STAT3-siRNA cells. Each color represents the small RNA tags</p><p> whose first base is a certain base. Most 22-nt small RNAs begin with the</p><p> base “U”. The 23-nt small RNAs display a bias to “A” and “U” at first base</p><p> in SW480/STAT3-siRNA while only “U” in SW480/siRNA-control. Figure S3. The proportions of unique common tags and total common tags of small</p><p>RNAs detected in SW480/siRNA-control and SW480/STAT3-siRNA</p><p> cells. The very few unique common tags indicate that SW480/STAT3-siRNA</p><p> presents a distinctive small RNA profile compared to SW480/siRNA-control. Figure S4. Mapping of small RNAs from SW480/siRNA-control and SW480/STAT3-</p><p> siRNA cells onto human chromosomes, respectively. Red lines indicate</p><p> miRNAs that are located on the antisense chains of genome while the blue</p><p> ones are on the sense chains.</p>