Table I.
Tumor-suppressor miRs.
| miR | Targets | Tumor | Impact on metastasis | Description |
|---|---|---|---|---|
| miR-15/16 | BCL2 | CLL | BCL2 repression by these microRNAs induces apoptosis in a leukemic cell line model | |
| COX-2 | Colon cancer | miR-16 as a central post-transcriptional regulator of COX-2 and shows the ability of elevated levels of HuR to antagonize miR-16 function | ||
| CHEK1 | Follicular lymphoma | Distinct microRNA profiles are associated with an increased proliferative capacity and a ‘late’ germinal center B-cell phenotype | ||
| CEBPβ, CDC25a, CCNE1 | Fibroblast | Upon cell cycle re-entry, the rapid decay of miR-16 alleviates repression of target genes, allowing proper resumption of the cell cycle | ||
| VEGF, VEGFR2, FGFR1 | Fibroblast | miR-16 plays important roles in regulating cell-intrinsic angiogenic activity of endothelial cells | ||
| FGF2, FGFR1 | Cancer-associated fibroblast | Down-regulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promotes tumor growth and progression | ||
| CCNE1 | miR-15 and miR-16 families as novel transcriptional targets of E2F, which, in turn, modulates E2F activity | |||
| FGFR1, PI3KCa, MDM4, VEGFa | Multiple myeloma | Deletion of miR-15/16 is commonly observed in early stages of multiple myeloma | ||
| WIP1 | Role of miR-16 in the regulation of Wip1 phosphatase in the DNA damage response and mammary tumorigenesis | |||
| BMI-1 | Ovarian cancer | Bmi-1 is down-regulated by miR-15a or miR-16 expression and leads to reduction in ovarian cancer cell proliferation and clonal growth | ||
| CCND1, CCND2, CCNE1 | Lung cancer | Overexpression of miR-15/16 induces arrest in G(1)-G(0) | ||
| miR-31 | ITGA5, RDX, RhoA, FZD3, M-RIP, MMP16 | Breast cancer | Suppresses | miR-31 uses multiple mechanisms to oppose metastasis |
| SATB2 | Cancer-associated fibroblast | New insights into tumor–stroma interaction and involvement of miR-31 in regulation of tumor cell motility | ||
| miR-34 | SIRT1 | Colon cancer | miR-34 suppression of SIRT1 leads to apoptosis only in colon cancer cells with wild-type p53 | |
| BCL2, NOTCH, HMGA2 | miR-34-mediated suppression of self-renewal is related to the direct modulation of the downstream targets Bcl-2, Notch, and HMGA2 | |||
| MYC | Fibroblast | During senescence, miR-34a targets the proto-oncogene MYC and co-ordinately controls a set of cell cycle regulators | ||
| AXL | Lung cancer | Axl receptor is regulated by miR-34a and miR-199a/b, suppressed by promoter methylation in solid cancer | ||
| MET | Ovarian cancer | MET is a critical effector of p53, and inhibition of MET may be an effective antimetastatic approach to treat cancers with p53 mutations | ||
| NANOG, SOX2, MYCN | Embryonic fibroblast | Suppression of reprogramming by miR-34a due to repression of pluripotency genes | ||
| SNAIL | Colon cancer | A new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs | ||
| miR-143/145 | KRAS, RREB1 | Pancreatic cancer | miR-143/miR-145 are suppressed by KRAS through RREB1, revealing a feed-forward mechanism that potentiates Ras signaling | |
| KRAS, MYC, CCND2, CDK6, E2F3 | Colon cancer | EGFR suppresses miR-143 and miR-145 in murine models of colon cancer | ||
| BCL2 | Cervical cancer | Promotion of apoptosis by miR-143 through the suppression of BCL2 | ||
| PAI1 | Bladder cancer | miR-145 and PAI1 as clinically relevant biomarkers in bladder cancer | ||
| PRC1, PLK1 | Liposarcoma | The down-regulation of PRC1 and its docking partner PLK1 suggests that miR-143 inhibits cytokinesis in these cells | ||
| MLL-AF4 | ALL | Therapeutic promise of up-regulating miR-143 expression for MLL-AF4 B-cell ALL | ||
| MMP-13 | Osteosarcoma | Down-regulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 up-regulation | ||
| ERK5 | Burkitt lymphoma | miRs-143 and -145 may be useful as biomarkers that differentiate B-cell malignant cells from normal cells | ||
| Let-7 family | KRAS | Lung cancer | The let-7 family negatively regulates let-60/RAS in C. elegans and lung tumors | |
| HMGA2 | Chromosomal translocations associated with human tumors disrupt repression of high mobility group A2 (Hmga2) by let-7 miRNA | |||
| MYC | Burkitt lymphoma | Dysregulation of let-7 participates in genesis and maintenance of Burkitt lymphoma and other MYC-dysregulated cancers | ||
| IMP-1 | Let-7-oncofetal proteins could be novel therapeutic targets and potential biomarkers for cancer treatment | |||
| DICER | Existence of a regulatory loop to regulate the equilibrated state of Dicer and various miRNAs | |||
| CDC-34 | Fibroblast | Let-7 represses Cdc34, stabilizes Wee1 kinase, and increases a fraction of cells in G(2)/M in primary fibroblasts | ||
| IL6 | Breast cancer | Inflammation activates a positive feedback loop that maintains the epigenetic transformed state | ||
| E2F2, CCND2 | Prostate cancer | Let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2 | ||
| BCL-XL | Liver cancer | Let-7 suppresses Bcl-xL expression in hepatocellular carcinomas and potentiates sorafenib-induced apoptosis | ||
| PLCγ1 | Breast cancer | Tumor-suppressor function by negatively regulating EGF-driven cell invasion, viability, and cell cycle progression in breast cancer | ||
| miR-200 family | ZEB1, ZEB2 | Breast cancer | Suppresses | Down-regulation of the miR-200 family may be an important step in tumor progression |
| ERRFI-1 | Bladder cancer | miR-200 is sufficient to restore EGFR dependency at least in some of the mesenchymal bladder cancer cells | ||
| ZEB1, CTNNB1 | Nasopharyngeal carcinoma | The inhibitory effects of miR-200a on cell growth, migration, and invasion are mediated by distinct targets and pathways | ||
| BMI-1 | Pancreatic cancer | ZEB1 links EMT and stemness maintenance by suppressing the miR-200 family and thereby promotes migration | ||
| PLCγ1 | Breast cancer | Tumor-suppressor function by negatively regulating EGF-driven cell invasion, viability, and cell cycle progression in breast cancer | ||
| FAP1 | miR-200c sensitizes cells to apoptosis mediated by CD95 | |||
| SUZ12 | Breast cancer | The miR-200b-Suz12-cadherin pathway is important for cancer stem cell growth and invasive ability | ||
| FLT1/VEGFR1 | Lung cancer | miR-200 suppresses lung adenocarcinoma metastasis by targeting Flt1 in tumor cells | ||
| JAG1, MALM2, MALM3 | These findings explain increased Notch signaling in some types of cancers, where mutations in Notch pathway genes are rare | |||
| FN1, LEPR, NTRK2, ARHGAP19 | Breast and endometrial cancer | miR-200c actively represses a program of mesenchymal and neuronal genes involved in cell motility and anoikis resistance | ||
| p38α | Ovarian cancer | miR-200a-dependent stress signature correlates with improved survival of patients in response to treatment |