GRB2 SOS1/2 SHC 1/2/3/4 PDGFR PDGF EGFR EGF PKC SPHK 1/2 RAS RAF1

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GRB2 SOS1/2 SHC 1/2/3/4 PDGFR PDGF EGFR EGF PKC SPHK 1/2 RAS RAF1 miR-27ab; miR-153; miR-141/200a; miR-124/506; miR-15/16/195/424/497; miR-128; miR-96/1271; miR-182; miR-338/338-3p; miR-150; miR-129/129-5p; miR-17-5p/20/93.mr/106/519.d; miR-203; miR-106/302; miR-183; miR-221/222; miR-22; miR-10; miR-199/199-5p; miR-125/351; miR-138 SOS1/2 SOS1: miR-217; miR-204/211; miR-27ab; miR-124/506; miR-148/152; miR-106/302; miR-128; miR-17-5p/20/93.mr/106/519.d; miR-200bc/429; miR-425/489; miR-181; miR-194; miR-365; miR-9; miR-132/212; miR-203; miR-1/206; miR-24; miR-155; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-15/16/195/424/497; miR-451; miR-103/107; miR-129/129-5p; miR-143; miR-101; miR-18ab; miR-375; miR-96/1271; miR-182; miR-23ab; miR-144; miR-455/455-5p; miR-125/351; miR-223 SOS2: miR-148/152; miR-129/129-5p; miR-130/301; miR-193ab; miR-499/499-5p; miR-199/199-5p; miR-21/590-5p; miR-124/506; miR-19; miR-138; miR-15/16/195/424/497; miR-208/208ab; miR-383; miR-204/211; miR-145; miR-214/761; miR-221/222; miR-96/1271; miR-182; miR-135 SHC 1/2/3/4 SHC1: miR-9; miR-204/211; miR-218; miR-124/506; miR-203; miR-139-5p; miR-18ab; miR-150; miR-200bc/429; miR-219/219-5p; miR-96/1271; miR-153; miR-365; miR-22; miR-216/216b; miR-375; miR-10; miR-7/7ab SHC2: miR-9; miR-338/338-3p; miR-218; miR-146 SHC3: miR-192/215; miR-338/338-3p SHC4: miR-129/129-5p; miR-106/302; miR-218; miR-200bc/429; miR-150; miR-182; miR-27ab; miR-203; miR-31; miR-140/140-5p/876-3p; miR-124/506; miR-216/216b; miR-208/208ab; miR-499/499-5p; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-96/1271; miR-101; miR-144; miR-216/216a; miR-128; miR-141/200a; miR-137; miR-155; miR-26ab/1297 PDGFR PDGF EGFR EGF miR-200bc/429; miR-204/211; miR-135; miR-218; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-182; miR-101; miR-96/1271; miR-1/206; miR-125/351; miR-205; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-214/761; miR-129/129-5p; miR-155; miR-103/107; miR-455/455-5p; miR-223; miR-181 DAG PKC SPHK 1/2 * SPHK1: miR-124/506; miR-1/206 SPHK2: miR-153; miR-130/301; miR-338/338-3p; miR-1/206; miR-19; miR-25/32/92/92ab/363/367; miR-184; miR-137; miR-181; miR-451; miR-503; miR-383; miR-15/16/195/424/497; miR-31 RAS KRAS: miR-181; miR-27ab; miR-143; miR-217; miR-96/1271; miR-132/212; miR-155; miR-193ab; miR-19; miR-365; miR-199/199-5p; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-141/200a; miR-216/216b; miR-1/206; miR-425/489; miR-129/129-5p; miR-214/761; miR-146; miR-383; miR-190; miR-204/211; miR-23ab; miR-15/16/195/424/497; miR-200bc/429; miR-216/216a; miR-125/351; miR-128; miR-101; miR-218; miR-31; miR-144; miR-7/7ab; miR-194; miR-142-3p; miR-490/490-3p HRAS: miR-338/338-3p RAF1 miR-7/7ab; miR-19; miR-15/16/195/424/497; miR-125/351; miR-135; miR-455/455-5p; miR-503; miR-139-5p; miR-150; miR-1/206; miR-143 MAP2K MAP2K1: miR-181; miR-15/16/195/424/497; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-148/152; miR-144; miR-96/1271; miR-130/301; miR-203; miR-503; miR-139-5p; miR-23ab MAP2K2: miR-503 MAPK1 miR-204/211; miR-128; miR-132/212; miR-23ab; miR-150; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-27ab; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-190; miR-214/761; miR-10; miR-187; miR-29abc; miR-216/216a; miR-15/16/195/424/497; miR-122; miR-9; miR-125/351 MSK1 miR-130/301; miR-128; miR-148/152; miR-17-5p/20/93.mr/106/519.d; miR-19; miR-27ab; miR-204/211; miR-203; miR-106/302; miR-18ab; miR-103/107; miR-1/206; miR-425/489; miR-144; miR-455/455-5p; miR-199/199-5p; miR-153; miR-129/129-5p; miR-23ab; miR-21/590-5p RASSF1 miR-181; miR-124/506; miR-96/1271; miR-10; miR-490/490-3p; miR-203; miR-193ab; miR-125/351 DAPK 1/2/3 DAPK1: miR-141/200a; miR-191; miR-26ab/1297; miR-130/301; miR-23ab; miR-143; miR-338/338-3p; miR-124/506; miR-7/7ab; let-7/98; miR-221/222; miR-204/211; miR-383 DAPK2: miR-214/761; miR-129/129-5p; miR-499/499-5p; miR-106/302; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; let-7/98; miR-138; miR-10; miR-17-5p/20/93.mr/106/519.d; miR-25/32/92/92ab/363/367; miR-133; miR-208/208ab; miR-143; miR-122; miR-205 DAPK3: miR-7/7ab; miR-503; miR-128; miR-214/761 miR-7/7ab; miR-27ab; miR-106/302; miR-141/200a; miR-133; miR-155; miR-101; miR-365; miR-455/455-5p; miR-1/206; miR-128; miR-103/107; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-129/129-5p; miR-144; miR-218 miR-499/499-5p; miR-199/199-5p; miR-150; miR-19; miR-145 PDGFA: miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-135; miR-1/206; miR-23ab; miR-196ab; miR-153; miR-221/222; miR-194; miR-141/200a; miR-375 PDGFB: miR-184; miR-17-5p/20/93.mr/106/519.d; let-7/98; miR-143; miR-29abc; miR-122; miR-204/211; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-31; miR-150; miR-139-5p; miR-19 PDGFRA: miR-141/200a; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-17-5p/20/93.mr/106/519.d; miR-146; miR-181; miR-33/33ab; miR-182; miR-219/219-5p; miR-218; miR-128; miR-27ab; miR-24; miR-137; miR-130/301; miR-29abc; miR-455/455-5p; miR-26ab/1297; miR-203; miR-140/140-5p/876-3p; miR-196ab; miR-96/1271; miR-204/211; miR-132/212; miR-375; miR-129/129-5p; miR-143; miR-25/32/92/92ab/363/367; miR-216/216a; miR-193ab; miR-10; miR-139-5p; miR-153; miR-499/499-5p; miR-9; miR-490/490-3p; miR-383; miR-122 PDGFRB: miR-24; miR-9; miR-204/211; miR-338/338-3p; miR-18ab; miR-30a/30a-5p/30b/30b-5p/30cde/384-5p; miR-29abc; miR-499/499-5p; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-146; miR-124/506; miR-17-5p/20/93.mr/106/519.d; miR-143; miR-129/129-5p; miR-19; miR-138; miR-365; miR-208/208ab; miR-141/200a; miR-31; miR-181; miR-193ab; miR-223; miR-150; miR-135; miR-122 miR-99ab/100; miR-194; miR-101; miR-145; miR-153; miR-31; miR-18ab; miR-23ab; miR-15/16/195/424/497; miR-22; miR-125/351; miR-503; miR-214/761; miR-24; miR-10; miR-132/212; miR-103/107; miR-29abc; miR-181; miR-19 FGFR3 FGF3 miR-425/489; miR-365; miR-33/33ab; miR-146 PLCG

Supplemental Figure 4. Overview of Growth Factor Receptor signaling. * PRKCA: miR-205; miR-203; miR-199/199-5p; miR-23ab; miR-223; miR-219/219-5p; miR-139-5p; miR-17-5p/20/93.mr/106/519.d; miR-132/212; miR-150; miR-200bc/429;miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-129/129-5p; miR-216/216b; miR-375; miR-15/16/195/424/497; miR-216/216a; miR-22; miR-338/338-3p; miR-141/200a; miR-9; miR-24; miR-183; miR-1/206; miR-193ab; miR-210; miR-125/351; miR-214/761; miR-10; miR-503; miR-181; miR-122; miR-146; miR-138; miR-194; miR-204/211; miR-490/490-3p; miR-192/215; miR-217; miR-7/7ab PRKCB1: miR-183; miR-129/129-5p; miR-203; miR-141/200a; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-194; miR-182; miR-26ab/1297; miR-106/302; let-7/98; miR-365; miR-184; miR-148/152; miR-33/33ab; miR-29abc; miR-7/7ab PRKCD: miR-26ab/1297; miR-181; miR-129/129-5p; miR-490/490-3p; miR-218; miR-27ab; miR-15/16/195/424/497 PRKCG: miR-338/338-3p; miR-503; miR-140/140-5p/876-3p; miR-135; miR-1/206 PRKCE: miR-31; miR-96/1271; miR-129/129-5p; miR-216/216a; miR-101; miR-141/200a; miR-146; miR-205; miR-103/107; miR-1/206; miR-33/33ab; miR-182; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-143; miR-223; miR-10; miR-181; miR-383; miR-144; miR-23ab; miR-22; miR-21/590-5p; miR-132/212; miR-218; miR-216/216b; miR-25/32/92/92ab/363/367; miR-139-5p; miR-106/302; miR-125/351; miR-29abc; miR-19 PRKCH: miR-24; miR-205; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-216/216a; miR-204/211; miR-27ab; miR-17-5p/20/93.mr/106/519.d; miR-145; miR-383; miR-216/216b; miR-221/222; miR-200bc/429; miR-455/455-5p; miR-214/761 PRKCI: miR-203; miR-455/455-5p; miR-103/107; miR-219/219-5p; miR-146; miR-365; miR-10; miR-155; miR-183; miR-199/199-5p; miR-23ab; miR-141/200a;miR-204/211;miR-15/16/195/424/497;miR-129/129-5p;miR-24;miR-33/33ab;miR-200bc/429;miR-96/1271;miR-29abc;miR-1/206;miR-150;miR-490/490-3p;miR-217;miR-138;miR-18ab;miR-216/216a;miR-182;miR-181 PRKCQ: miR-26ab/1297; miR-34a/34b-5p/34c/34c-5p/449/449abc/699; miR-192/215; miR-25/32/92/92ab/363/367; miR-203; miR-183; miR-193ab; miR-221/222; miR-137; miR-31; miR-214/761; miR-383; miR-200bc/429 PRKCZ: miR-148/152; miR-15/16/195/424/497; miR-338/338-3p; miR-503 Supplemental Figure 4. Overview of Growth Factor Receptor signaling. Summary of Growth Factor Receptor signaling and predicted miRNA interactions. miRNAs that were described to be downregulated in bladder cancer are highlighted in green, while upregulated miRNAs are highlighted in red; all other potential interactions are highlighted in black. Target interactions were predicted with TargetScan 5.1. miRNAs presented in this figure are all highly conserved among vertebrates; for a list of other miRNAs see Supplemental Table 5.