Table 3.
Correlations of miRNA with gene expression (Spearman correlation test, p-value < 0.05).
| miRNAs Associated with Longer TTBM | |||
|---|---|---|---|
| miR-30b-3p | BM promoting genes: inverse correlation | ||
| RANKL | rho = −0.33; p = 0.002 | miR-30 family inhibits BM in BC by targeting CXCL8 [36] | |
| ITGA3 | rho = −0.31; p = 0.003 | ||
| TCF7 | rho = −0.25; p = 0.018 | ||
| CD44 | rho = −0.24; p = 0.021 | ||
| CXCL8 | rho = −0.21; p = 0.045 | ||
| miR-139-3p | BM protective genes: positive correlation | ||
| NOTCH1 | rho = 0.29; p = 0.005 | ||
| BMPR2 | rho = 0.27; p = 0.011 | ||
| BM promoting genes: inverse correlation | |||
| TCF7 | rho = −0.23; p = 0.027 | ||
| ITGA3 | rho = −0.22; p = 0.038 | ||
| miR-204-5p | BM protective genes: positive correlation | ||
| FOS | rho = 0.28; p = 0.007 | ||
| BMPR2 | rho = 0.32; p = 0.003 | ||
| SATB2 | rho = 0.34; p = 0.001 | ||
| SMAD4 | rho = 0.35; p = 0.001 | ||
| BM promoting genes: inverse correlation | |||
| CD44 | rho = −0.55; p < 0.001 | miR-204 regulates RUNX2 expression and MSC differentiation [85]. | |
| RANKL | rho = −0.42; p < 0.001 | Sponging of miR-204-5p by lncRNA SNHG4 upregulates RUNX2 and promotes tumor progression in RCC [86]. | |
| ITGA3 | rho = −0.42; p < 0.001 | miR-204-5p inhibits TGF-β-induced IL11 production in BM cells of BC [59]. | |
| RUNX2 ° | rho = −0.41; p < 0.001 | miR-204 inhibits growth and motility of CRC cells by CXCL8 downregulation [87]. | |
| ITGA5 | rho = −0.36; p = 0.001 | ||
| CDH11 ° | rho = −0.39; p < 0.001 | ||
| TGFB1 | rho = −0.33; p = 0.002 | ||
| CXCL8 | rho = −0.3; p = 0.005 | ||
| TCF7 | rho = −0.36; p < 0.001 | ||
| CTGF | rho = −0.26; p = 0.014 | ||
| miR-542-5p | BM protective genes: positive correlation | ||
| SATB2 | rho = 0.34; p = 0.001 | miR-542-5p increases SMAD2 expression levels in ICU weakness [88]. | |
| SMAD2 | rho = 0.29; p = 0.006 | ||
| BM promoting genes: inverse correlation | |||
| TCF7 | rho = −0.37; p < 0.001 | ||
| RUNX2 | rho = −0.31; p = 0.003 | ||
| CD44 | rho = −0.32; p = 0.002 | ||
| CXCR4 | rho = −0.21; p = 0.044 | ||
| miRNAs Associated With Shorter TTBM | |||
| miR-21-5p | BM protective genes: inverse correlation | ||
| SATB2 | rho = −0.22; p = 0.04 | ||
| SMAD4 | rho = −0.24; p = 0.026 | ||
| BM promoting genes: positive correlation | |||
| TCF7 | rho = 0.27; p = 0.011 | ||
| CD44 * | rho = 0.25; p = 0.018 | ||
| ITGA3 | rho = 0.29; p = 0.005 | ||
| miR-21-3p | BM protective genes: inverse correlation | ||
| FOS | rho = −0.45; p < 0.001 | miR-21 deficiency results in cFOS upregulation in periodontal tissues [89]. | |
| BMPR2 | rho = −0.42; p < 0.001 | BMPR2 is directly targeted by miR-21 in PC cells [90]. | |
| SATB2 | rho = −0.31; p = 0.003 | miR-21-3p is involved in proliferation and invasion through SMAD4/Erk signaling in CRC [31]. | |
| SMAD4 | rho = 0.22; p = 0.043 | ||
| BM promoting genes: positive correlation | |||
| ITGA3 | rho = 0.42; p < 0.001 | TGFB1 signaling increases miR-21 expression in renal fibrosis [91]. | |
| RANKL | rho = 0.38; p < 0.001 | ||
| CD44 * | rho = 0.37; p < 0.001 | ||
| TGFB1 | rho = 0.25; p = 0.018 | ||
| CXCL8 * | rho = 0.22; p = 0.043 | ||
| miR-28-3p | BM protective genes: inverse correlation | ||
| SATB2 | rho = −0.24; p = 0.022 | ||
| SRCIN1 | rho = −0.22; p = 0.038 | ||
| BM promoting genes: positive correlation | |||
| CXCR4 | rho = 0.24; p = 0.025 | ||
| miR-34c-5p | BM protective genes: inverse correlation | ||
| SATB2 ° | rho = −0.23; p = 0.033 | miR-34s inhibit osteoblast proliferation and differentiation in mouse by targeting SATB2 [92]. | |
| FOS | rho = −0.26; p = 0.015 | SATB2 targeted by miR-34c-5p suppresses proliferation and metastasis attenuating EMT in CRC [39]. | |
| BM promoting genes: positive correlation | |||
| CD44 | rho = 0.3; p = 0.004 | ||
| ITGA3 | rho = 0.38; p < 0.001 | ||
| RANK | rho = 0.21; p = 0.047 | ||
| TGFB1 | rho = 0.26; p = 0.015 | ||
| miR-23a-3p | BM protective genes: positive correlation | ||
| BMPR2 * | rho = 0.23; p = 0.027 | ||
| BM promoting genes: inverse correlation | |||
| CXCL8 * | rho = −0.25; p = 0.017 | ||
| ELK1 | rho = −0.24; p = 0.021 | ||
| miR-20a-5p | BM protective genes: inverse correlation | ||
| OPG * | rho = −0.21; p = 0.044 | ||
| BM protective genes: positive correlation | |||
| PDCD4 ° | rho = 0.28; p = 0.009 | ||
| BM promoting genes: inverse correlation | |||
| ITGB3 | rho = −0.23; p = 0.03 | ||
| BM promoting genes: positive correlation | |||
| IL11 | rho = 0.27; p = 0.011 | RUNX2 is positively correlated with miR-20a-5p in adipose SC during osteogenic differentiation [93]. | |
| TCF7 | rho = 0.26; p = 0.012 | ||
| RUNX2 | rho = 0.22; p = 0.035 | ||
| miR-335-3p | BM protective genes: inverse correlation | ||
| OPG | rho = −0.23; p = 0.03 | ||
| BM promoting genes: positive correlation | |||
| CD44 | rho = 0.31; p = 0.003 | ||
| ITGA5 | rho = 0.29; p = 0.007 | ||
| RANKL | rho = 0.22; p = 0.04 | ||
| CDH11 | rho = 0.36; p = 0.001 | ||
| ITGA3 | rho = 0.27; p = 0.011 | ||
| TGFB1 | rho = 0.29; p = 0.006 | ||
| TCF7 | rho = 0.35; p = 0.001 | ||
| RUNX2 | rho = 0.3; p = 0.004 | ||
| miR-182-5p | BM protective genes: inverse correlation | ||
| SATB2 *,° | rho = −0.29; p = 0.006 | microRNA-182 targets SATB2 to promote CRC proliferation and metastasis [94]. | |
| BMPR2 * | rho = −0.28; p = 0.009 | ||
| OPG | rho = −0.28; p = 0.007 | ||
| BM promoting genes: positive correlation | |||
| CD44 | rho = 0.37; p < 0.001 | ||
| CDH11 * | rho = 0.25; p = 0.02 | ||
| ITGA3 | rho = 0.37; p < 0.001 | ||
| IL11 * | rho = 0.21; p = 0.046 | ||
| CXCL8 | rho = 0.32; p = 0.002 | ||
| TCF7 | rho = 0.34; p = 0.001 | ||
| RUNX2 | rho = 0.27; p = 0.011 | ||
| miR-27a-3p | BM protective genes: inverse correlation | ||
| BMP7 * | rho = −0.29; p = 0.007 | ||
| BM protective genes: positive correlation | |||
| PDCD4 | rho = 0.23; p = 0.031 | ||
| BM promoting genes: inverse correlation | |||
| CXCL8 * | rho = −0.26; p = 0.013 | ||
BM protective genes: SATB2, BMP7, SMAD4, PDCD4, BMPR2, OPG, NOS3, SMAD2, NOTCH1, FOS, SRCIN1. BM promoting genes: TCF7, DKK1, CD44, ITGA3, CTGF, IL11, CXCL8, RANKL, RUNX2, CDH11, TGFB1, CXCR4, SMAD1, TGIF2, RANK, ELK1, ITGB3, ITGA5. * = listed in DIANA-TarBase v.8 of validated miRNA-target pairs [16]. ° = predicted miRNA target through miRDB.org [17]. Note: miRNA correlated to TTBM and not to TTMOTB are highlighted in bold. Correlations with similar literature findings are highlighted in bold. Abbreviations: miRNA = microRNA, TTBM = time to bone metastasis, miR = microRNA, BM = bone metastasis, BC = breast cancer, MSC = mesenchymal stem cells, lncRNA = long non-coding RNA, SNHG4 = small nucleolar RNA host gene 4, RCC = renal cell carcinoma, CRC = colorectal cancer, PC = prostate cancer, EMT = epithelial-mesenchymal transition, RCC = renal cell carcinoma, SC = stem cells.