Table 2.
Epigenome regulators targeted by microRNAs in breast cancer.
| microRNA | miRNA acts as a Tumor Suppressor or Oncogenic miRNA (OncomiR) | Target (alias) | Function of Target in Citation | Reference |
|---|---|---|---|---|
| miR-7 | Tumor suppressor miRNA | KMT1E (SETDB1) | Promotes STAT3 expression which drives c-MYC, TWIST, and miR-9 expression in BCSCs | [107] |
| miR-7 | Tumor suppressor miRNA | KMT5A (SETD8) | Drives DNA double stranded breaks and promotes DNA repair | [108] |
| miR-10b | OncomiR | HDAC4 | Promotes tamoxifen sensitivity; enhances tamoxifen-induced apoptosis | [109] |
| miR-17 | Tumor suppressor miRNA | KAT13B (NCOA3) | Promotes taxol resistance by increasing Bcl-2 expression | [110] |
| miR-17-5p | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances E2F1- and estrogen receptor-mediated gene expression | [111] |
| miR-17-5p | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-20b | Tumor suppressor miRNA | KAT13B (NCOA3) | Promotes taxol resistance by increasing Bcl-2 expression | [110] |
| miR-22 | OncomiR | HDAC4 | Transcriptional repressor of p21 and p27; Regulates sensitivity to fulvestrant | [113] |
| miR-22 | OncomiR | KAT5 (TIP60) | Involved in the inhibition of EMT; Decreases cell migration and invasion | [114] |
| miR-22 | Tumor suppressor miRNA | KDM7B (PHF8) | Promotes EMT; Binds to transcriptional start site of, and activates, SNAI1; Drives cell proliferation, migration, and tumor growth | [115] |
| miR-22 | Tumor suppressor miRNA | SIRT1 | Promotes proliferation, migration, and invasion; Inhibits senescence | [116,117] |
| miR-22 | OncomiR | TET1 | Promotes global 5hmC levels | [70] |
| miR-22 | OncomiR | TET2 | Promotes global 5hmC levels; Inhibits cell migration, EMT, and mammosphere formation; Promotes miR-200 family expression | [70] |
| miR-22 | OncomiR | TET3 | Promotes global 5hmC levels; Inhibits cell migration, EMT, and mammosphere formation; Promotes miR-200 family expression | [70] |
| miR-23a | Tumor suppressor miRNA | KDM4A (JMJD2A) | Promotes transient site-specific copy gains; Drives drug resistance through expression of CKS1B | [92] |
| miR-23b | Tumor suppressor miRNA | KDM4A (JMJD2A) | Promotes transient site-specific copy gains | [92] |
| miR-25 | OncomiR | KAT3B (EP300) | Inhibits EMT through increased E-cadherin expression; Blocks drug- and irradiation-induced senescence | [118] |
| miR-26a | Tumor suppressor miRNA | KMT6A (EZH2) | Inhibits apoptosis; Promotes anchorage-independent growth and tumorigenesis | [87] |
| miR-26b | Tumor suppressor miRNA | KMT6A (EZH2) | Promotes tumor aggressiveness and the inflammatory phenotype | [88] |
| miR-29a | OncomiR | TET1 | Inhibits cell proliferation, migration, and EMT | [71] |
| miR-29b | OncomiR | TET1 | Inhibits cell proliferation, anchorage-independent growth, migration, and EMT; Binds to the promoter region of the ZEB2 | [72] |
| miR-29b-5p | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-34a | Tumor suppressor miRNA | HDAC1 | Deacetylates HSP70 K246; Promotes cancer cell survival and drug resistance by inhibiting autophagic cell death | [119] |
| miR-34a | Tumor suppressor miRNA | HDAC7 | Deacetylates HSP70 K246; Promotes cancer cell survival and drug resistance by inhibiting autophagic cell death | [119] |
| miR-34a | Tumor suppressor miRNA | SIRT1 | Promotes expansion of BCSCs; Drives tumor growth | [120] |
| miR-92b | Tumor suppressor miRNA | KMT6A (EZH2) | Blocks rapamycin-induced autophagy; Enhances cell viability and invasion | [89] |
| miR-93 | OncomiR | KAT3B (EP300) | Inhibits EMT through increased E-cadherin expression; Blocks drug- and irradiation-induced senescence | [118] |
| miR-101 | Tumor suppressor miRNA | KMT6A (EZH2) | Drives a metastatic tumor phenotype, oncogenic gene expression, and cell invasion | [121] |
| miR-106a | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-106b | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-106b | OncomiR | KAT3B (EP300) | Inhibits EMT through increased E-cadherin expression; Blocks drug- and irradiation-induced senescence | [118] |
| miR-125a-5p | Tumor suppressor miRNA | HDAC4 | Promotes cell proliferation, migration, and invasion; Decreases expression of HDAC5 and HDAC7 | [122] |
| miR-125a-5p | Tumor suppressor miRNA | HDAC5 | Drives cell proliferation, migration, and invasion; Decreases apoptosis by deacetylating RUNX3 and reduces RUNX3-p300 complex binding to target promoters | [123] |
| miR-128 | Tumor suppressor miRNA | SIRT1 | Deacetylates p53 and suppresses its transcriptional targets; Increases Akt signaling; Protects against apoptosis by decreasing PUMA expression | [124] |
| miR-137 | Tumor suppressor miRNA | KAT13A (NCOA1) | Accelerates proliferation; Decreases cell viability | [112] |
| miR-137 | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-137 | Tumor suppressor miRNA | KAT13C (NCOA2) | Accelerates proliferation; Decreases cell viability | [112] |
| miR-137 | Tumor suppressor miRNA | KDM4A (JMJD2A) | Promotes transient site-specific copy gains | [92] |
| miR-137 | Tumor suppressor miRNA | KDM5B (JARID1B) | Drives cell proliferation and migration | [94] |
| miR-138 | Tumor suppressor miRNA | KDM5C (JARID1C) | Drives cell proliferation | [94] |
| miR-138 | Tumor suppressor miRNA | KDM6B (JMJD3) | Promotes cell proliferation, invasion, and EMT through H3K27me3 demethylation | [125] |
| miR-138 | Tumor suppressor miRNA | KMT6A (EZH2) | Drives cell invasion EMT, and primary tumor growth | [126] |
| miR-143 | Tumor suppressor miRNA | DNMT3A | Accelerates cell proliferation and anchorage-independent growth; Hypermethylates PTEN and TNFRSF10C | [52] |
| miR-148 | n/a | DNMT3B | n/a; Only studied binding of miR-148 of different DNMT3B splice variants in normal and cancer cells | [54] |
| miR-148a | Tumor suppressor miRNA | DNMT1 | Promotes cell proliferation, colony formation, and tumor angiogenesis; Drives IGF-IR and IRS1 expression, and promotes Akt and ERK signaling by hypermethylating miR-148a; Suppresses ER-α expression | [127,128] |
| miR-152 | Tumor suppressor miRNA | DNMT1 | Promotes cell proliferation, colony formation, and tumor angiogenesis; Drives IGF-IR and IRS1 expression, and promotes Akt and ERK signaling by hypermethylating miR-152 | [127] |
| miR-185 | Tumor suppressor miRNA | DNMT1 | Drives cell proliferation; Silences BRCA1 expression by hypermethylation | [129] |
| miR-199 | Tumor suppressor miRNA | KMT6A (EZH2) | Accelerates cell proliferation and promotes invasion | [86] |
| miR-200a | Tumor suppressor miRNA | SIRT1 | Promotes cellular transformation, anchorage-independent growth and migration; Binds to miR-200a promoter and recruits DNMT1, 3A, and 3B to suppress expression | [130] |
| miR-200b | Tumor suppressor miRNA | DNMT3A | Binds, along with c-MYC, to the miR-200b promoter to silence expression and drive EMT | [53] |
| miR-200b | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-200b | Tumor suppressor miRNA | SUZ12 | Promotes formation and maintenance of mammospheres, as well as tumor growth and the maintenance of CSCs through H3K27me3 and recruitment of PcG suppression of E-cadherin | [131] |
| miR-200c | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-211-5p | Tumor suppressor miRNA | SETBP1 | Promotes cell proliferation, invasion, and migration, as well as metastasis | [132] |
| miR-214 | Tumor suppressor miRNA | KMT6A (EZH2) | Accelerates cell proliferation and promotes invasion | [86] |
| miR-221 | OncomiR | DNMT3B | Inhibits stemness by repressing Nanog and Oct3/4 expression | [51] |
| miR-222 | OncomiR | DNMT3B | Inhibits stemness by repressing Nanog and Oct3/4 expression | [51] |
| miR-340 | Tumor suppressor miRNA | KMT6 (EZH2) | Drives cell proliferation, invasion, migration, and induces apoptosis via DNMT1 expression and decreased miR-200a/b expression | [133] |
| miR-342 | OncomiR | DNMT1 | Binds to ID4 promoter for normal breast function and development | [134] |
| miR-381-3p | Tumor suppressor miRNA | KMT1E (SETDB1) | Drives cell proliferation, cell cycle progression and migration; Accelerates primary tumor growth | [135] |
| miR-448 | Tumor suppressor miRNA | KDM5B (JARID1B) | Enhances proliferation, anchorage-independent growth, migration, invasion, and promotes a stem-like phenotype via induction of lncRNA MALAT1 | [93] |
| miR-491-5p | Tumor suppressor miRNA | KDM4B (JMJD2B) | Suppresses estrogen receptor-mediated signaling and cell proliferation | [136] |
| miR-502 | Tumor suppressor miRNA | KMT5A (SETD8) | Promotes cell cycle progression, migration, invasion, and EMT | [137] |
| miR-519d | Tumor suppressor miRNA | KAT13B (NCOA3) | Accelerates proliferation; enhances estrogen receptor-mediated gene expression | [112] |
| miR-590-3p | Tumor suppressor miRNA | SIRT1 | Drives cell survival; Inhibits apoptosis; Prevents acetylation and activation of p53 | [138] |
| miR-708 | Tumor suppressor miRNA | KDM1A (LSD1) | Promotes cell proliferation and invasion | [91] |
| miR-1307-3p | OncomiR | SMYD4 | Suppresses cell proliferation and anchorage-independent growth; Inhibits tumor formation | [139] |
| miR-1915-3p | Tumor suppressor miRNA | KMT2F (SETD1A) | Drives estrogen receptor-mediated signaling through H3K4 methylation; Enhances cell proliferation and migration; Suppresses apoptosis | [140] |
| miR-3666 | Tumor suppressor miRNA | SIRT7 | Promotes cell proliferation; Inhibits apoptosis | [141] |