Regulatory Mechanism of MicroRNA Expression in Cancer
Abstract
:1. Introduction
2. miRNA Deregulation in Cancer
3. Dysregulation of miRNA Transcription in Cancer
3.1. Modulation of miRNA Expression by Transcription Factors in Cancer
3.2. Aberrant miRNA Expression by DNA Methylation Modification in Cancer
4. Dysregulation of Pri-miRNA Processing in Cancer
4.1. Dysregulation of the Microprocessor in Cancer
4.2. Dysregulation of the Microprocessor-Associated Proteins in Cancer
4.3. Dysregulation of pri-miRNA Editing in Cancer
5. Dysregulation of Pre-miRNA Processing in Cancer
5.1. Defect in Pre-miRNA Export in Cancer
5.2. Dysregulation of DICER1 and TARBP2 in Cancer
5.3. Dysregulation of AGO2 in Cancer
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
mRNA | Messenger RNA |
miRNA | MicroRNA |
pri-miRNA | Primary-microRNA |
pre-miRNA | Precursor-microRNA |
XPO5 | Exportin 5 |
AGO2 | Argonaute 2 |
TNRC6A | Trinucleotide Repeat Containing Adaptor 6A |
RISC | RNA-induced Silencing Complex |
miRISC | miRNA-induced silencing complex |
3′-UTR | 3′- Untranslated Region |
DNA | Deoxyribonucleic Acid |
CLL | Chronic Lymphocytic Leukemia |
BCL2 | B-cell Lymphoma 2 |
MDS | Myelodysplastic syndrome |
AML | Acute Myeloid Leukemia |
RREB1 | Ras Responsive Element Binding Protein 1 |
C/EBPβ | Ras Responsive Element Binding Protein 1 |
C/EBPβ | CCAAT-enhancer-binding Protein Beta |
TCF4 | Transcription Factor 4 |
FOXO1 | Forkhead Box Protein O1 |
FOXO3 | Forkhead Box Protein O3 |
MN1 | Meniongoma-1 |
E2F1 | E2F Transcription Factor 1 |
CTGF | Connective Tissue Growth Factor |
THBS1 | Thrombospondin 1 |
PTEN | Phosphatase and Tensin Homolog |
HIF1-α | Hypoxia-inducible Factor 1-alpha |
ZEB | Zinc Finger E-box-binding Homeobox 1 |
EMT | Epithelial-Mesenchymal Transition |
NRs | Nuclear Receptors |
ER | Estrogen Receptor |
GR | Glucocorticoid Receptor |
MR | Mineralocorticoid Receptor |
NCoR/SMRT | Nuclear Receptor co-repressor/ Silencing Mediator of Retinoic |
SK1 | Sphingosine Kinase 1 |
ChIP | Chromatin Immunoprecipitation |
BCL6 | B-cell Lymphoma 6 |
CDK6 | Cyclin-dependent Kinase 6 |
SOX4 | SRY-Box Transcription Factor 4 |
CDH1 | Cadherin-1 |
TET | Ten-eleven Translocation Methylcytosine Dioxygenase |
PLAG | Pleomorphic adenoma gene |
CREB | cAMP-response element binding |
DGCR8 | DiGeorge Critical Region 8 |
ssRNA | Single-stranded RNA |
dsRNA | Double-stranded RNA |
dsRBD1 | dsRNA Binding Domain1 |
DDX5 | DEAD-box Helicases p68 |
DDX17 | DEAD-box Helicases p72 |
YAP | Yes-associated Protein |
NF90/NF45 | Nuclear Factor 90/45 |
ADAR | Adenosine Deaminases Acting on RNA |
RAN-GTP | RAs-related Nuclear protein-GTP |
TARBP2 | Tar RNA-Binding Protein 2 |
CRISPR | Clustered Regularly Interspaced Short Palindromic Repeats |
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Regulation of miRNA Expression by DNA Binding Factor | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
Transcriptional activation by p53 | miR-34a, miR-34b miR-34c | Cell cycle arrest, apoptosis & senescence | Various types of cancers | [26] |
miR-145 | Apoptosis | Various cancers like prostate cancer | [33,34] | |
Transcriptional repression by RREB1 | miR-143/145 cluster | Transcriptional repression of miR-143/145 cluster | Various cancers like Pancreatic, Colorectal Adenocarcinoma | [35] |
Regulation by C/EBPβ, beta-catenin/TCF4, FOXO1 & FOXO3 | miR-145 | Various cancers like Renal cancer | [36,37] | |
Regulation by MN1 | miR-20a, miR-181b | Inverse correlation between MN1 and miRNAs | acute myeloid leukemia (AML) patients | [38] |
Transcriptional activation by Myc | miR-17~92 cluster | Controls the expression of E2F1, THBS1, CTGF, & PTEN | Various types of cancer, including B- Cell lymphoma & Breast cancer | [39,40,41,42,43] |
miR-200c, miR-26, miR-29, miR-30, let-7 | Suppresses the expression of their genes | Nasopharyngeal carcinoma & Lymphoma | [44,45,46,47] | |
HIF1α | miR-210 | Repression of initiation of tumor growth | Various cancers like Head & neck tumor | [48] |
miR-155 | [49] | |||
ZEB1 & ZEB2 | miR-200 family | Various cancers | [50] | |
Repression by ER | miR-221/222 | Suppression of miR-221/222 expression by NcoR/SMRT complex | Breast cancer | [51] |
miR-515 | Increased levels of oncogenic SK1 | Breast cancer | [52] | |
Androgen/AR | miR-125b, miR-21, miR-221/222, miR-27a, miR-32 | Oncogenic role | Prostate cancer & Hematological malignancies | [53] [54,55] |
miR-135a, miR-141 | Tumor suppressive role | Prostate cancer | [56,57] | |
Progesterone receptor /PR | miR-141, miR-23, miR-320, let-7 | Breast & ovarian cancer | [58,59,60,61] | |
Glucocorticoids/ GR | miR-15, miR-16, miR-223 | Incresead expression of miRNA | Leukemia cell lines | [62] |
Regulation of miRNA Expression by Epigenetic Alteration | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
Promoter hypermethylation | miR-127 | Increassed expression of BCL6 | Bladder Cancer | [63] |
Promoter hypermethylation | miR-124-1 | Activation of , CDK6 | Breast, Colon, Liver, Leukemias & Lymphomas | [64,65] |
Promoter hypermethylation | miR-129-2 | Upregulation of SOX4 | Endometrial Gastric cancer | [66] |
Promoter hypermethylation | miR-34a miR-34b/c | Gastric, Prostate & Colon cancer | [67,68] | |
CpG methylation | miR-200 | Inactivation | Bladder, breast, non-small lung cancer, leukemia | [69,70,71] |
The Microprocessor in Cancer | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
Up/downregulation of DROSHA | Global miRNA expression | Cancer progression & poor patient survival | Cervical carcinoma, Wilms tumor | [86,87] |
Drosha E147K mutation | Global miRNA expression | Reduced function | Wilms tumors | [88,89,90,91] |
Upregulation of DGCR8 expression | Global miRNA expression | Dysregulation is associated with poor patient survival | Esophageal, Bladder, Prostate & ovarian cancer | [92] |
E518K mutation in the dsRBD1 domain of DGCR8 | Decrease of crucial miRNAs | Wilms tumors | [89,91] | |
Regulation of Microprocessor in Cancer | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
NF90/NF45 | pri-let-7, pri-miR-7-1 | Inhibits the processing | Hepatocellular carcinoma | [93,94] |
Pre-miRNA Export in Cancer | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
Mutations of XPO5 | Global miRNA expression | Accumulation of pre-miRNA in the nucleus | Sporadic colon cancer, Gastric & Endometrial cancer | [95] |
Phosphorylation of XPO5 at Thr345, Ser416, and Ser497 | Global miRNA expression | Correlates with global miRNA downregulation and with poor survival in patients | Hepatocellular carcinoma, | [96] |
DICER1 and TARBP2 in Cancer | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
Mutations of DICER1 | Global miRNA expression | Somatic and germline DICER1 mutations lead to defective pre-miRNA processing | Pleuropulmonary blastoma, Rhabdomyosarcoma, non-epithelial ovarian cancers, liver tumor | [97,98,99,100,101,102] |
Mutations within the RNase IIIb domain of DICER1 | 5p miRNAs | Deregulation of pre miRNA expression | Various cancer like ovarian cancer | [92,103] |
TARBP2 Deletion | Global miRNA expression | Adenoid cystic carcinoma | [104] | |
Upregulation of TARBP2 expression | Melanoma, breast & prostate cancer | [105] | ||
Frameshift mutations of TARBP2 | Global miRNA expression | Reduced levels of DICER1 and mature miRNAs | Sporadic & hereditary carcinomas | [106,107] |
AGO2 in Cancer | ||||
Factor | miRNA | Mechanism/Function/ Clinical Correlation | Cancer Type | References |
AGO2 expression dysregulation | oncomiRs | Repression of the targets of oncomiRs | Breast, gastric, head & neck cancers | [108,109,110,111] |
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Ali Syeda, Z.; Langden, S.S.S.; Munkhzul, C.; Lee, M.; Song, S.J. Regulatory Mechanism of MicroRNA Expression in Cancer. Int. J. Mol. Sci. 2020, 21, 1723. https://doi.org/10.3390/ijms21051723
Ali Syeda Z, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory Mechanism of MicroRNA Expression in Cancer. International Journal of Molecular Sciences. 2020; 21(5):1723. https://doi.org/10.3390/ijms21051723
Chicago/Turabian StyleAli Syeda, Zainab, Siu Semar Saratu’ Langden, Choijamts Munkhzul, Mihye Lee, and Su Jung Song. 2020. "Regulatory Mechanism of MicroRNA Expression in Cancer" International Journal of Molecular Sciences 21, no. 5: 1723. https://doi.org/10.3390/ijms21051723