An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer
Abstract
:1. Introduction
2. Relevant Quadruplex Structures Involved in Cancer
2.1. DNA G4s
2.1.1. DNA G4s Related to Telomeric Function
2.1.2. DNA G4s in Oncogenes
2.1.3. DNA G4s in Tumor Suppressors
2.1.4. DNA G4s in Other Genomic Elements
2.2. RNA G4s
2.2.1. RNA G4s Related to Telomeric Function
2.2.2. RNA G4s in UTRs
2.2.3. RNA G4s in Splicing Sites
2.2.4. RNA G4s in Non-Coding RNAs
2.3. i-Motifs
2.3.1. Telomeric i-Motifs
2.3.2. Extra-Telomeric i-Motifs
3. Therapeutic Relevance of Quadruplex Structures in Cancer
4. Future Perspectives and Conclusions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
C | Cytosine |
G | Guanine |
G4 | G-quadruplex |
HQ | DNA:RNA hybrid G-quadruplex |
lncRNA | Long non-coding RNA |
miRNA | MicroRNA |
NHE | Nuclear hypersensitivity element |
Nt | Nucleotide |
UTR | Untranslated region |
TSS | Transcription start site |
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Gene | DNA G4 | RNA G4 | i-Motif | Gene | DNA G4 | RNA G4 | i-Motif |
---|---|---|---|---|---|---|---|
ADAM10 | No | Not specified [30] | No | MT3-MMP | No | Not specified [31] | No |
BAG1 | No | Not specified [32] | No | Mitochondrial | Antiparallel [33] | No | No |
BCL2 | Mixed [34] | Not specified [35] | Not specified [36] | n-MYC | No | No | Not specified [37] |
BCLX | No | Parallel [38] | No | n-RAS | Not specified [39] | Not specified [40] | No |
CCND3 | No | Parallel [41] | No | PARP1 | 3+1 Hybrid [42] | No | No |
CD133 | Mixed [43] | No | No | PDGFa | Parallel [44] | No | No |
c-KIT | Mixed [45] | No | No | PDGFRb | Parallel [46] | No | Not specified [47] |
c-MYB | Tetrad:heptad [48] | No | No | PIM1 | No | Parallel [49] | No |
c-MYC | Parallel [50] | No | Fold-back [51] | RB | Antiparallel [52] | No | Not specified [52] |
CXCL14 | No | Parallel [53] | No | Ribosomal | Parallel [54] | No | No |
ESR1 | No | Parallel [55] | No | RET | Parallel [56] | No | Not specified [56] |
EWSR1 | No | Parallel [57] | No | SMARCA4 | No | No | Not specified [58] |
FGFR2 | Parallel [59] | No | No | STAT3 | Parallel [60] | No | No |
GSEC | No | Not specified [61] | No | TAOK2 | No | Parallel [53] | No |
HIF1a | Parallel [62] | No | No | Telomeres | Antiparallel [63] | No | Not specified [64] |
HNF4a | No | Parallel [65] | No | TERRA | No | Mixed [13] | No |
h-RAS | Mixed [39] | Not specified [39] | Not specified [66] | TGFb2 | No | Parallel [67] | No |
hTERT | Parallel [68] | Parallel [69] | No | TP53 | No | Not specified [70] | No |
k-RAS | Mixed [71] | Not specified [72] | Not specified [73] | TRF2 | No | Not specified [74] | No |
L1 | No | Not specified [75] | No | VEGF | Parallel [76] | Not specified [77] | Antiparallel [78] |
miRNA-149 | No | Parallel [79] | No | VEGFR2 | Antiparallel [80] | No | No |
miRNA-1587 | No | Parallel [81] | No | WT1 | Parallel [82] | No | No |
miRNA-26a | No | Not specified [83] | No | YY1 | No | Mixed [84] | Not specified [84] |
miRNA-3620-5p | No | Parallel [85] | No | ZIC1 | No | Parallel [86] | No |
miRNA-92b | No | Not specified [87] | No |
Compound | Quadruplex Target | Antitumoral Effect |
---|---|---|
BRACO-19 | Telomeric DNA G4s | Interference with hTERT [172] |
Telomeric i-Motifs | Interference with hTERT [170] | |
CX-3543 | Ribosomal DNA G4s | Inhibition of RNA Polymerase I [175] |
CX-5461 | Multiple DNA G4s | Synthetic lethality in BRCA deficient tumors [174] |
PBP1, PBP2 | BCL2 DNA G4 (PBP2) | Downregulate BCL2 expression [173] |
BCL2 i-Motif (PBP1) | Upregulate BCL2 expression [173] | |
Pyridostatin | Multiple DNA G4s | Growth arrest by inducing DNA damage [171] |
RNA G4 | Regulates alternative splicing of EWSR1 [57] | |
Telomeric i-Motif | Interference with hTERT [170] | |
TMPyP4 | Telomeric DNA G4 | Interference with hTERT [167] |
Telomeric RNA G4 | Interference with hTERT [168] | |
Telomeric i-Motif | Interference with hTERT [169] |
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Sanchez-Martin, V.; Lopez-Pujante, C.; Soriano-Rodriguez, M.; Garcia-Salcedo, J.A. An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer. Int. J. Mol. Sci. 2020, 21, 8900. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238900
Sanchez-Martin V, Lopez-Pujante C, Soriano-Rodriguez M, Garcia-Salcedo JA. An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer. International Journal of Molecular Sciences. 2020; 21(23):8900. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238900
Chicago/Turabian StyleSanchez-Martin, Victoria, Carmen Lopez-Pujante, Miguel Soriano-Rodriguez, and Jose A. Garcia-Salcedo. 2020. "An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer" International Journal of Molecular Sciences 21, no. 23: 8900. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238900