Table 1.
Targets of oncogenic miRNAs and their role in cancer cells.
| miRNAs | Target gene | Techniques | Short description | References |
|---|---|---|---|---|
| miR-21 | TPM1 | WB, LA | miR-21 downregulates TPM1 in breast cancer and leads to anchorage-independent growth. | [25] |
| E2F1 | WB, RT-PCR | miR-21 regulates E2F1 by TGF-β signaling pathway. | [55] | |
| TGFBR2 | WB, RT-PCR | miR-21 regulates TGFBR2 by TGF-β signaling pathway. | [55] | |
| TIMP3 | WB, RT-PCR | TIMP3 is a MMP inhibitor, miR-21 suppresses TIMP3 by promoting invasiveness of cancer cells. | [56] | |
| SERPINB5 | WB, LA | Downregulation of PDCD4 and maspin (SERPINB5) by miR-21 causes tumorogenesis. | [57] | |
| PDCD4 | WB, RT-PCR, LA | miR-21 decreases PDCD4 protein amounts and increases invasion. | [58] | |
| FAS, CDK6, PDCD4, CDKN1A, FAM3C, HIPK3, PRRG4, ACTA2, BTG2, BMPR2, SESN1, IL6R, SOCS5, GLCCI1, APAF1, SLC16A10, SGK3, RP2, CFL2 |
RT-PCR, M | Inhibition of miR-21 in MCF-7 breast cancer cells shows reduced expression of p53 tumor suppressor protein. FAS, CDK6, CDKN1A, FAM3C, HIPK3, PRRG4, ACTA2, BTG2, BMPR2, SESN1, IL6R and tumor suppressor protein Programmed Cell Death 4 (PDCD4) are also downregulated by miR-21. | [30] | |
| FAS, TIMP3 | WB, LA | Downregulation of miR-21 increases Fas ligand and TIMP3 expression; thereby it is involved in the upregulation of apoptosis. | [59] | |
| CDC25A | WB, RT-PCR, LA | miR-21 suppresses Cdc25A expression, a cell cycle regulator. | [60] | |
| RECK | RT-PCR | miR-21 suppresses RECK and inhibitors of MMPs and thus promotes invasiveness of cancer cells. | [56] | |
| MTAP | LA | Apoptotic function of MTAP is suppressed by miR-21. | [61] | |
| RECK | WB, RT-PCR, LA | RECK regulating the membrane-anchored protease is down regulated by miR-21. | [62] | |
| PDCD4 | WB, LA | miR-21 positively regulates PDCD4 through interaction with ovarian steroids and TGF-β signaling pathway. | [55] | |
| BTG2 | EGFP, WB, Fluorescence Intensity | Expression of miR-21 leads to lower level of BTG2 which is a cell cycle regulator and tumor suppressor. It causes loss of control on G1 to S phase transition. | [63] | |
| PTEN | LA | miR-21 regulates MMP-2 expression in cardiac fibroblasts of the infarct zone via PTEN pathway. | [64] | |
| BTG2 | WB, RT-PCR, LA | miR-21 directly inhibits BTG2 which is a cell cycle inhibitor leading to uncontrolled DNA synthesis by activation of forkhead box M1. | [65] | |
| PELI1 | RT-PCR, LA | miR-21 overexpression inhibits Peli1 via kappaB signalling. | [66] | |
| PDCD4 | WB | Deregulation of miR-21 by vinyl carbamate induces mouse lung tumorigenesis by down regulating PDCD4. | [67] | |
| BIG-H3 | LA | miR-21 targets big-h3. It could be induced by TGF-β and it regulates TGF-β signalling positively and negatively. | [68] | |
| BIM | WB, LA | Bim, a apoptotic activator, is collectively targeted by miR-21, miR-24, and miR-221 and its action is suppressed. | [69] | |
| HER2 | WB, RT-PCR | miR-21 upregulates human epidermal growth factor receptor 2 and acts as oncogene. | [34] | |
| MSH2, SMAD7 | WB, RT-PCR, LA | miR-21 downregulates MSH2 and SMAD7 in TGF-β pathway and causes breast cancer progression. | [33] | |
|
| ||||
| miR-10b | HOXD10 | WB, LA | Overexpression of miR-10b induces robust invasion and metastasis by down regulating translation of homeobox D10. | [37] |
| KLF4 | WB, RT-PCR, LA | miR-10b reduces endogenous KLF4 protein, a tumor suppressor. | [70] | |
| SFRS1 | WB, RT-PCR, LA | miR-10b suppresses SFRS1 (SR-family splicing factor) and causes migration, invasion, and in vivo metastasis of neuroblastoma cells. | [71] | |
| SFRS10 | LA | miR-10b suppresses SFRS10 and causes migration, invasion, and in vivo metastasis of neuroblastoma cells. | [71] | |
|
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| miR-125a-5p | ERBB2 | WB, RT-PCR, LA | Expression of either miR-125a or miR-125b results in suppression of ERBB2 and ERBB3 (oncogene family) and exhibits reduced migration and invasion capacities. | [72] |
| TP53 | WB, RT-PCR, LA | miR-125b inhibits p53 gene translationally and transcriptionally and the isomer of miRNA-125 (miRNA-125a) translationally arrests mRNA of the p53, a tumor suppressor gene. | [44] | |
| HuR | WB, RT-PCR, LA | HuR is a stress induced RNA binding protein having over expression in different cancers. Expression of miR-125a significantly reduces HuR. | [73] | |
| ARID3B | WB | ARID3B is overexpressed in human ovarian cancer. Overexpression of miR-125a induces conversion of highly invasive ovarian cancer cells from a mesenchymal to an epithelial morphology and suppresses cancer by negatively regulating EMT. | [74] | |
|
| ||||
| miR-125b | BAK1 | WB, RT-PCR, LA, M | Overexpression of miR-125b stimulates androgen-independent growth of prostate cancer by down regulating Bak1 (proapoptotic regulator). | [75] |
| CDK6, CDC25A | WB | miR-125b overexpression decreases CDK6 and CDC25A expression. It regulates proliferation of U251 glioma stem cells through cell cycle regulated proteins CDK6 and CDC25A. | [76] | |
| SMO | WB, RT-PCR, LA | Downregulation of miR-125b allows high levels of Hedgehog-dependent gene expression leading to tumor cell proliferation by allowing Hedgehog signalling. | [77] | |
| ST18 | WB, Branched, LA, DNA Probe Assay | ST18 is downregulated in DS-AMKL patients having high expression of miR-125b; thus miR-125b-2 acts as a positive regulator of megakaryopoiesis. | [78] | |
| DICER1 | WB, LA, Branched DNA Probe Assay | DICER1 is down regulated in DS-AMKL patients having high expression of miR-125b, thus miR-125b-2 acts as a positive regulator of megakaryopoiesis. | [78] | |
| TP53INP1 | LA | miR-125b directly represses TP53INP1, an apoptosis regulator in p53 pathway. | [79] | |
| BMF | WB, RT-PCR, LA | overexpression of miR-125b reduces expression of cell apoptosis related protein Bcl-2 modifying factor (Bmf), by targeting BMF. | [80] | |
| BMPR1B | LA | miR-125b targets BMPR1B and causes risk in breast cancer pathogenesis. | [81] | |
| HuR | WB | HuR is a stress-induced RNA binding protein having over expression in different cancers. miR-125a targets HuR. | [82] | |
| κB-Ras2 | LA | miR-125b downregulates kappaB-Ras2 gene expression. | [83] | |
| E2F3 | WB, RT-PCR, LA | E2F3, an inducer of bladder cancer, is suppressed by miR-125b at protein level through regulation of G1/S transition through the E2F3-Cyclin A2 signaling pathway. | [84] | |
| PUMA | LA | miR-125b directly represses Puma, an apoptosis regulator in p53 pathway. | [79] | |
| BAK1, CDC25C, PPP1CA, PPP2CA, PRKRA, TDG,TP53, ZAC1 |
LA | miR-125b directly represses apoptosis regulators such as BAK1, CDC25C, PPP1CA, PRKRA and TP53A, ZAC1, in p53 pathway. | [79] | |
| PPP2CA | RT-PCR, LA | miR-125b directly inhibits apoptosis by down regulating PPP2CA expression. | [85] | |
| TDG | qRT-PCR | miR-125b directly suppresses the expression of TDG in p53 pathway. | [86] | |
|
| ||||
| miR-155 | CYR61 | WB, RT-PCR, LA | overexpression of miR-155 contributes to preeclampsia development by targeting and downregulating angiogenic regulating factor CYR61. | [87] |
| FOXO3 | WB, RT-PCR, LA | Inverse correlation between miR-155 and FOXO3a prevails in breast cancer cell lines and tumors. | [47] | |
| SOCS1 | Immunofluorescence, RT-PCR, LA | Overexpression of miR-155 in breast cancer cells leads to constitutive activation of signal transducer and activator of transcription 3 (STAT3) through the Janus-activated kinase (JAK) pathway. | [88] | |
| CCND1 | LA | miR-155 reduces endogenous expression of CCND1 by suppressing Luc-CCND1. | [89] | |
| IKBKE | WB, RT-PCR, LA | miR-155 expression is increased in gastric epithelial cell lines and gastric mucosal tissues. miR-155 negatively regulates IkappaB kinase epsilon, Sma- and Mad-related protein 2 (SMAD2), Fas-associated death domain protein, interleukin-8, and growth-related oncogene-alpha. |
[90] | |
| FADD | WB, RT-PCR | miR-155 expression is increased in gastric epithelial cell lines and gastric mucosal tissues. miR-155 negatively regulates IkappaB kinase epsilon, Sma- and Mad-related protein 2 (SMAD2), Fas-associated death domain protein, interleukin-8, and growth-related oncogene-alpha. |
[90] | |
| JARID2 | WB, RT-PCR, LA | overexpression of miR-155 decreases levels of endogenous JARID2, cell cycle regulator mRNA and causes tumor. | [91] | |
| CEBPB | WB, RT-PCR, LA | EBPβ translation is suppressed by miR-155 through C/EBPβ in tumor-activated monocytes and reduces tumor progression. | [92] | |
| SHIP | WB, RT-PCR, LA | miR-155 decreases SHIP1 expression as a result of autocrine stimulation by proinflammatory cytokine tumor necrosis factor alpha (TNF-α). | [93] | |
| TAM | WB, RT-PCR | miR-155 downregulates TAM and causes spontaneous breast cancer development. | [94] | |
| VHL | WB, RT-PCR | miR155 downregulates VHL, tumor suppressor via promoting HIF transcription factors and angiogenesis. | [95] | |
| p53 | WB, RT-PCR, LA | miR155 downregulates p53 and promotes cell proliferation. | [52] | |
| VHL | WB, RT-PCR, LA | miR155 downregulates VHL and promotes lymph node metastasis and poor prognosis as well as triple-negative tumor in breast cancer. | [54] | |
| CDC73 | WB, RT-PCR, LA | miR155 negatively regulates CDC73 which inturn positively regulates β-catenin, cyclin D1, and c-MYC and increases cell viability. | [53] | |
| ZNF652 | WB, RT-PCR | miR155 downregulates ZNF652 causing expression of TGFB1, TGFB2, TGFBR2, EGFR, SMAD2, and VIM resulting in increased cell invasion and metastasis. | [96] | |
| MMP2, MMP9, VEGF | WB, RT-PCR | miR155 causes up regulation of MMP2, MMP9, and VEGF resulting in increased tumor size. | [97] | |
| HK2 | WB, RT-PCR, LA | miR155 up regulates hk2 by activating signal transducer and activator of transcription 3 (STAT3 ) and targeting C/EBPβ. | [48] | |
WB: Western blot; RT-PCR: real time-PCR; LA: luciferase Assay; M: microarray.