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					                                                                                                              Supplementary Table 2: miRNAs in bladder cancer, page - 1 -


Supplementary Table 2
Deregulated miRNAs and their function in bladder cancer
Abbrevations: FFPE: Formalin-fixed, paraffin-embedded; for gene symbols see text or Entrez Gene (http://www.ncbi.nlm.nih.gov/sites/entrez).
                        a                                                                 b                                           c
Sample characteristics: Matched pairs of tumor tissue and normal adjacent control tissue. Tissue from tumors with stage Ta/T1/T2-4. Bladder cancer
                     d                                                                                                                                e
tissue/normal tissue. Low grade tumor tissue/high grade tumor tissue/invasive tumor tissue/normal adjacent control tissue/disease free control tissue. Tissue
                                           f
from tumors with stage Ta/Tis/T1/T2-4/Tx. Urine from patients with infected bladders/G1 bladder tumors/G2-3 bladder tumors/healthy controls.
References to the studies: see at the end of this Supplementary Table or the corresponding references in the text of the manuscript.

                                                                                                                                                    Diagnostic/
                                  Ref. No.              Patients/
No.   miRNA       Study                      Material                               Expression            Regulation      Function        Target    prognostic
                                  in Text               Samples
                                                                                                                                                    impact
                                                                                    Downregulated in
                                             Frozen             a
1     let-7a      Wang et al.     82                         7/7                    tumor tissue vs.
                                             tissue
                                                                                    normal tissue
                                                                                    Downregulated in
                  Friedman et                                       a
2     miR-1                       85         NA             37/37                   tumor tissue vs.
                  al.
                                                                                    normal tissue
                                             Frozen                     b                                                                           Marker for
3     miR-7a      Veerla et al.   89                       7/10/17
                                             tissue                                                                                                 FGFR3 status
                                                                                    Upregulated in
                                             FFPE                   a               metastatic tissue
4     miR-10b     Baffa et al.    88                        10/10
                                             tissue                                 vs. primary tumor
                                                                                    tissue
                                                                                    Upregulated in
                  Gottardo et                Frozen                 c
5     miR-17-5p                   80                         25/2                   tumor tissue vs.
                  al.                        tissue
                                                                                    normal tissue
                                                                                    Upregulated in high
                                             Frozen                             d                                                                   Prognostic
6     miR-21      Catto et al.    86                    22/12/18/10/10              grade and invasive
                                             tissue                                                                                                 marker
                                                                                    bladder
                                                                                                                                                    Ratio of miR-
                                                                                    Upregulated in                                                  21/miR-205
                                             FFPE                           e       invasive tumors vs.                                             higher in
7     miR-21      Neely et al.    90                     22/1/5/24/1
                                             tissue                                 non-invasive                                                    invasive tumors
                                                                                    tumors                                                          vs. non-invasive
                                                                                                                                                    tumors
                                                                                                         Supplementary Table 2: miRNAs in bladder cancer, page - 2 -


                                                                                                                                               Diagnostic/
                                  Ref. No.              Patients/
No.   miRNA       Study                      Material                           Expression          Regulation         Function       Target   prognostic
                                  in Text               Samples
                                                                                                                                               impact
                                                                                Upregulated in
                  Gottardo et                Frozen                 c
8     miR-23a                     80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Upregulated in
                  Gottardo et                Frozen                 c
9     miR-23b                     80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Upregulated in
                  Gottardo et                Frozen                 c
10    miR-26b                     80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Upregulated in
                                             FFPE                   a           metastatic tissue
11    miR-29b     Baffa et al.    88                        10/10
                                             tissue                             vs. primary tumor
                                                                                tissue
                                                                                Downregulated in
                  Dyrskjot et                Frozen                     c                                                                      Prognostic
12    miR-29c                     84                       106/11               tumor tissue vs.
                  al.                        tissue                                                                                            marker
                                                                                normal tissue
                                                                                Downregulated in
                  Friedman et                                       a
13    miR-29c                     85         NA             37/37               tumor tissue vs.
                  al.
                                                                                normal tissue
                                                                                Downregulated in
      miR-30-a-                              Frozen                     a
14                Ichimi et al.   81                       104/104              tumor tissue vs.                       Cell growth    KRT7
      3p                                     tissue
                                                                                normal tissue
                                                                                Downregulated in
                                             Frozen             a
15    miR-30c     Wang et al.     82                         7/7                tumor tissue vs.
                                             tissue
                                                                                normal tissue
                  Lodygin et                                                                        Promotor
16    miR-34a                     68
                  al.                                                                               hypermethylation
                                             Frozen                         d   Downregulated in    Promotor                                   Prognostic
17    miR-99a     Catto et al.    86                    22/12/18/10/10                                                                FGFR3
                                             tissue                             low-grade tumors    hypermethylation                           marker
                                             Frozen                         d   Downregulated in    Promotor                                   Prognostic
18    miR-100     Catto et al.    86                    22/12/18/10/10                                                                FGFR3
                                             tissue                             low-grade tumors    hypermethylation                           marker
                                                                                Downregulated in                     Proliferation,
                  Friedman et                                       a                               Promotor
19    miR-101                     85         NA             37/37               tumor tissue vs.                     colony           EZH2
                  al.                                                                               hypermethylation
                                                                                normal tissue                        formation
                                                                                                           Supplementary Table 2: miRNAs in bladder cancer, page - 3 -


                                                                                                                                                 Diagnostic/
                                  Ref. No.              Patients/
No.   miRNA       Study                      Material                           Expression             Regulation         Function      Target   prognostic
                                  in Text               Samples
                                                                                                                                                 impact
                                                                                Upregulated in
                  Gottardo et                Frozen                 c
20    miR-103-1                   80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Downregulated in
                                             Frozen                     a
21    miR-125b    Ichimi et al.   81                       104/104              tumor tissue vs.
                                             tissue
                                                                                normal tissue
                                                                                Upregulated in
                                                                                                                                                 Diagnostic
                                                                            f   bladder cancer
22    miR-126     Hanke et al.    30         Urine        7/11/11/11                                                                             marker (relative
                                                                                patients vs. healthy
                                                                                                                                                 to miR-512)
                                                                                controls
                                                                                Downregulated in
                  Dyrskjot et                Frozen                     c
23    miR-126*                    84                       106/11               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Downregulated in
                  Friedman et                                       a
24    miR-127                     85         NA             37/37               tumor tissue vs.
                  al.
                                                                                normal tissue
                                             Frozen                                                    Promotor
25    miR-127     Saito et al.    38
                                             tissue                                                    hypermethylation
                                                                                Downregulated in
                  Dyrskjot et                Frozen                     c                                                 Proliferation GALNT1, Prognostic
26    miR-129                     84                       106/11               tumor tissue vs.
                  al.                        tissue                                                                       and apoptosis SOX4    marker
                                                                                normal tissue
                                                                                Downregulated in
                                             Frozen                     a
27    miR-133a    Ichimi et al.   81                       104/104              tumor tissue vs.                          Cell growth   KRT7
                                             tissue
                                                                                normal tissue
                  Dyrskjot et                Frozen                     c       Upregulated in                                                   Prognostic
28    miR-133b                    84                       106/11
                  al.                        tissue                             progressing tumors                                               marker
                                                                                Downregulated in
                  Dyrskjot et                Frozen                     c
29    miR-141                     84                       106/11               T2-4 tumors vs. Ta
                  al.                        tissue
                                                                                tumors
                                                                                Upregulated in
      miR-142-                               FFPE                   a           metastatic tissue
30                Baffa et al.    88                        10/10
      5p                                     tissue                             vs. primary tumor
                                                                                tissue
31    miR-143     Lin et al.      83                                                                                      Cell growth   RAS
                                                                                                          Supplementary Table 2: miRNAs in bladder cancer, page - 4 -


                                                                                                                                                 Diagnostic/
                                Ref. No.              Patients/
No.   miRNA     Study                      Material                           Expression              Regulation      Function        Target     prognostic
                                in Text               Samples
                                                                                                                                                 impact
                                                                              Downregulated in
                Friedman et                                       a
32    miR-143                   85         NA             37/37               tumor tissue vs.
                al.
                                                                              normal tissue
                                                                              Downregulated in
                                           FFPE                   a
33    miR-143   Baffa et al.    88                        10/10               metastatic tumors
                                           tissue
                                                                              vs. primary tumors
                                                                              Downregulated in
                                           Frozen                     a
34    miR-145   Ichimi et al.   81                       104/104              tumor tissue vs.
                                           tissue
                                                                              normal tissue
                                                                              Downregulated in
                Dyrskjot et                Frozen                 c
35    miR-145                   84                       106/11               tumor tissue vs.
                al.                        tissue
                                                                              normal tissue
                                                                              Downregulated in
                Friedman et                                       a
36    miR-145                   85         NA             37/37               tumor tissue vs.
                al.
                                                                              normal tissue
                                                                              Downregulated in
                                           FFPE                   a           metastatic tissue
37    miR-145   Baffa et al.    88                        10/10
                                           tissue                             vs. primary tumor
                                                                              tissue
                                                                              Expressed in
                                                                              normal urothelium
                                                                              and in T1
                                           Bladder                            carcinoma cells
                                                                                                                                      CBFB,
                Ostenfeld                  tissue                         b   with lower intensity,
38    miR-145                   94                     182/101/34                                                     Apoptosis       PPP3CA
                et al.                     microarr                           in high grade
                                                                                                                                      , CLINT1
                                           ay                                 tumors expression
                                                                              lost in large areas
                                                                              with small areas
                                                                              with great intensity
                                                                              Upregulated in
                Friedman et                                       a
39    miR-182                   85         NA             37/37               tumor tissue vs.
                al.
                                                                              normal tissue
                                                                                                           Supplementary Table 2: miRNAs in bladder cancer, page - 5 -


                                                                                                                                                 Diagnostic/
                                  Ref. No.              Patients/
No.   miRNA       Study                      Material                           Expression             Regulation      Function        Target    prognostic
                                  in Text               Samples
                                                                                                                                                 impact
                                                                                Upregulated in
                                                                                                                                                 Diagnostic
                                                                            f   bladder cancer
40    miR-182     Hanke et al.    30         Urine        7/11/11/11                                                                             marker (relative
                                                                                patients vs. healthy
                                                                                                                                                 to miR-512)
                                                                                controls
                                                                                Upregulated in
                  Friedman et                                       a
41    miR-183                     85         NA             37/37               tumor tissue vs.
                  al.
                                                                                normal tissue
                                                                                Upregulated in
                  Gottardo et                Frozen                 c
42    miR-185                     80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                Downregulated in
                                             Frozen                     a
43    miR-195     Ichimi et al.   81                       104/104              tumor tissue vs.
                                             tissue
                                                                                normal tissue
                                                                                Upregulated in
                                                                                                                                                 Diagnostic
                                                                            f   bladder cancer
44    miR-199a    Hanke et al.    30         Urine        7/11/11/11                                                                             marker (relative
                                                                                patients vs. healthy
                                                                                                                                                 to miR-512)
                                                                                controls
                                                                                Downregulated in
                                             Frozen                     a
45    miR-199a*   Ichimi et al.   81                       104/104              tumor tissue vs.                       Cell growth     KRT7
                                             tissue
                                                                                normal tissue
                                                                                                                       MET/EMT,
                                                                                                                       migration,
                                                                                                                       reversion of
46    miR-200b/c Adam et al.      96                                                                                                   ERRFI1
                                                                                                                       an EGFR-
                                                                                                                       resistant
                                                                                                                       phenotype
                                                                                Downregulated in
                  Dyrskjot et                Frozen                     c
47    miR-200c                    84                       106/11               T2-4 tumors vs. Ta
                  al.                        tissue
                                                                                tumors
                                                                                Downregulated in
                  Gottardo et                Frozen                 c
48    miR-203                     80                         25/2               tumor tissue vs.
                  al.                        tissue
                                                                                normal tissue
                                                                                                               Supplementary Table 2: miRNAs in bladder cancer, page - 6 -


                                                                                                                                                     Diagnostic/
                                   Ref. No.              Patients/
No.   miRNA        Study                      Material                               Expression            Regulation      Function        Target    prognostic
                                   in Text               Samples
                                                                                                                                                     impact
                                                                                                                                                     Ratio of miR-
                                                                                     Downregulated in                                                21/miR-205
                                              FFPE                           e       invasive tumors vs.                                             higher in
49    miR-205      Neely et al.    90                     22/1/5/24/1
                                              tissue                                 non-invasive                                                    invasive tumors
                                                                                     tumors                                                          vs non-invasive
                                                                                                                                                     tumors
                                                                                     Upregulated in
                   Gottardo et                Frozen                 c
50    miR-205                      80                         25/2                   tumor tissue vs.
                   al.                        tissue
                                                                                     normal tissue
                                                                                     Upregulated in
                   Gottardo et                Frozen                 c
51    miR-221                      80                         25/2                   tumor tissue vs.
                   al.                        tissue
                                                                                     normal tissue
52    miR-221      Lu et al.       95                                                                                      Apoptosis       CDKN1B
                                                                                     Upregulated in
                   Gottardo et                Frozen                 c
53    miR-223                      80                         25/2                   tumor tissue vs.
                   al.                        tissue
                                                                                     normal tissue
                                                                                     Upregulated in
                   Friedman et                                       a
54    miR-224                      85         NA             37/37                   tumor tissue vs.
                   al.
                                                                                     normal tissue
                                                                                     Downregulated in
                                              FFPE                   a
55    miR-320      Baffa et al.    88                        10/10                   metastatic tumors
                                              tissue
                                                                                     vs. primary tumors
                                                                                     Upregulated in high
                                              Frozen                             d                                                                   Prognostic
56    miR-373      Catto et al.    86                    22/12/18/10/10              grade and invasive
                                              tissue                                                                                                 marker
                                                                                     bladder cancer
                                              Frozen                     b           positive in lymph                                               Prognostic
57    miR-452*     Veerla et al.   89                       7/10/17
                                              tissue                                 nodes                                                           marker
                                              Frozen                     b           positive in lymph                                               Prognostic
58    miR-452*     Veerla et al.   89                       7/10/17
                                              tissue                                 nodes                                                           marker
                   Dyrskjot et                Frozen                     c           Upregulated in                                                  Prognostic
59    miR-518c*                    84                       106/11
                   al.                        tissue                                 progressing tumors                                              marker

References
Adam, L. et al. miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor
 receptor therapy. Clin. Cancer Res. 15, 5060-5072 (2009).
                                                                                                  Supplementary Table 2: miRNAs in bladder cancer, page - 7 -


Baffa, R. et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J. Pathol. 219, 214-221 (2009).
Catto, J. W. et al. Distinct microRNA alterations characterize high- and low-grade bladder cancer. Cancer Res. 69, 8472-8481 (2009).
Dyrskjot, L. et al. Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. Cancer Res. 69,
  4851-4860 (2009).
Friedman, J. M. et al. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer
  Res. 69, 2623-2629 (2009).
Gottardo, F. et al. Micro-RNA profiling in kidney and bladder cancers. Urol. Oncol. 25, 387-392 (2007).
Hanke, M. et al. A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol.
  Oncol. doi:10.1016/j.urolonc.2009.01.027
Ichimi, T. et al. Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int. J. Cancer 125, 345-352 (2009).
Lin, T. et al. MicroRNA-143 as a tumor suppressor for bladder cancer. J. Urol. 181, 1372-1380 (2009).
Lodygin, D. et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 7, 2591-2600 (2008).
Lu, Q. et al. MicroRNA-221 silencing predisposed human bladder cancer cells to undergo apoptosis induced by TRAIL. Urol. Oncol.
  doi:10.1016/j.urolonc.2009.06.005
Neely, L. A. et al. A microRNA expression ratio defining the invasive phenotype in bladder tumors. Urol. Oncol. 28, 39-48 (2010).
Ostenfeld, M. S. et al. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature
  present in Ta bladder tumors. Oncogene 29, 1073-1084 (2010).
Saito, Y. et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells.
  Cancer Cell 9, 435-443 (2006).
Veerla, S. et al. MiRNA expression in urothelial carcinomas: Important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis,
  and frequent homozygous losses of miR-31. Int. J. Cancer 124, 2236-2242 (2009).
Wang, G. et al. Up-regulation of microRNA in bladder tumor tissue is not common. Int. Urol. Nephrol. doi:10.1007/s11255-009-9584-3

				
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