Introduction
Class | Symbol | Characteristic | Disease / biological function associations | |
---|---|---|---|---|
Small non-coding RNAs
|
MicroRNAs
| miRNAs | 18–25 nt; account 1–2% of the human genome; control the 50% of protein-coding genes; guide suppression of translation; Drosha and Dicer dependent small ncRNAs | initiation of various disorders including many, if not all, cancers / regulation of proliferation, differentiation, and apoptosis involved in human development |
Small interfering RNAs
| siRNAs | 19–23 nt; made by Dicer processing; guide sequence specific degradation of target mRNA | great potential in diseases treatment / posttranscriptional gene silencing mainly through RISC degradation mechanism; defence against pathogenic nucleic acids | |
Piwi-interacting RNAs
| piRNAs | 26–30 nt; bind Piwi proteins; Dicer independent; exist in genome clusters; principally restricted to the germline and somatic cells bordering the germline | relationship between piRNAs and diseases has not yet been discovered / involved in germ cell development, stem self-renewal, and retrotransposon silencing | |
Small nucleolar RNAs
| snoRNAs | 60–300 nt; enriched in the nucleolus; in vertebrate are excised from pre-mRNA introns; bind snoRNP proteins | association with development of some cancers / important function in the maturation of other non-coding RNAs, above all, rRNAs and snRNAs; miRNA-like snoRNAs regulate mRNAs | |
Promoter-associated small RNAs
| PASRs | 20–200 nt; modified 5′ (capped) ends; coincide with the transcriptional start sites of protein- and non-coding genes; made from transcription of short capped transcripts | relationship with diseases has not yet been discovered / involved in the regulation of the transcription of protein-coding genes by targeting epigenetic silencing complexes | |
Transcription initiation RNAs
| tiRNAs | ~ 18 nt ; have the highest density just downstream of transcriptional start sites; show patterns of positional conservation; preferentially located in GC-rich promoters | ||
Centromere repeat associated small interacting RNAs
| crasiRNAs | 34–42 nt; processed from long dsRNAs | relationship between crasiRNAs and diseases has not yet been discovered / involved in the recruitment of heterochromatin and/or centromeric proteins | |
Telomere-specific small RNAs
| tel-sRNAs | ~ 24 nt; Dicer independent; 2′-O-methylated at the 3′ terminus; evolutionarily conserved from protozoa to mammals; have not been described in human up to now | relationship between tel-sRNAs and diseases has not yet been discovered / epigenetic regulation | |
Pyknons
| subset of patterns of variable length; form mosaics in untranslated and protein-coding regions; more frequently in 3′ UTR | expected association with cancer biology / possible link with posttranscriptional silencing of genes, mainly involved in cell communication, regulation of transcription, signaling, transport, etc. | ||
Long non-coding RNAs
|
Long intergenic non-coding RNAs
| lincRNAs | ranging from several hundreds to tens of thousands nts; lie within the genomic intervals between two genes; transcriptional cis-regulation of neighbouring genes | involved in tumorigenesis and cancer metastasis / involved in diverse biological processes such as dosage compensation and/or imprinting |
Long intronic non-coding RNAs
| lie within the introns; evolutionary conserved; tissue and subcellular expression specified | aberrantly expressed in human cancers / possible link with posttranscriptional gene silencing | ||
Telomere-associated ncRNAs
| TERRAs | 100 bp - >9 kb; conserved among eukaryotes; synthesized from C-rich strand; polyadenylated; form inter-molecular G-quadruplex structure with single-stranded telomeric DNA | possible impact on telomere-associated diseases including many cancers / negative regulation of telomere length and activity through inhibition of telomerase | |
Long non-coding RNAs with dual functions
| both protein-coding and functionally regulatory RNA capacity | deregulation has been described in breast and ovarian tumors / modulate gene expression through diverse mechanisms | ||
Pseudogene RNAs
| gene copies that have lost the ability to code for a protein; potential to regulate their protein-coding cousin; made through retrotrans-position; tissue specific | often deregulated during tumorigenesis and cancer progression / regulation of tumor suppressors and oncogenes by acting as microRNA decoys | ||
Transcribed-ultraconserved regions
| T-UCRs | longer than 200 bp; absolutely conserved between orthologous regions of human, rat, and mouse; located in both intra- and intergenic regions | expression is often altered in some cancers; possible involvement in tumorigenesis / antisense inhibitors for protein-coding genes or other ncRNAs |
Small non-coding RNAs
MicroRNAs
MiRNA | Associated cancers | In vitro confirmed gene targets |
---|---|---|
MiR-21
| CRC, PC, RCC, GBM, BrC, NSCLC, BCL, PTC, HCC, HNSCC, ESCC, GC, CML, CCC, MM, OC, M, LC, PDA | PDCD4, TIMP3, RhoB, Spry1, PTEN, TM1, CDK2AP1, ANP32A, SMARCA4, ANKRD46, THRB, Cdc25A, BMPRRII, LRRFIP1, BTG2, MARCKS, TPM1 |
MiR-155
| NSCLC, SCLC, HCC, BrC, M, CCC, HL, PDA, RCC, GBM, PTC, CML, CRC, SPA, AML, NPC, CLL | FOXO3A, SOX6, SATB1, SKI, Wee1, SOCS1, SHIP1, S/EBPβ, IFN-γRα, AGTR1, FGF7, ZNF537, ZIC3, IKBKE, RhoA, BACH1, ZIC3, HIVEP2, CEBPB, ZNF652, ARID2, SMAD5, TP53INP1 |
MiR-145
| BrC, CRC, ESCC, NSCLC, PC, BCL, OC, GC, BlC, NPC, HCC | c-Myc, ERK5, FSCN1, SMAD2/3, IGF-1R, FLI1, DFF45, mucin 1, MYO6, CBFB, PPP3CA, CLINT1, ICP4, RTKN |
MiR-221
| BrC, PC, CRC, M, GBM, ALL, HCC, PTC, PDA, GC, CML, NSCLC, AML, OC | DVL2, KIT, CDKN1B, Bmf, p27, HOXB5, CDKN1C/p57, CDKN1B/p27, MMP1, SOD2, TIMP3, Dicer1, ERα, ARHI, PUMA, p27Kip1, p57 |
MiR-222
| ||
Let-7a
| M, HL, nHL, CRC, SLC, NSCLC, GC, HNSCC, ESCC, OC, CLL, HCC | PRDM-1, STAT3, Caspase-3, Integrin β3, PRDM1/blimp-1 |
MiR-16
| LC, OC, NPC, GC, PC, BrC, HCC, MM, CLL, HL | VEGFR2, FGFR1, Zyxin, Cyclin E1, Bmi-1, BRCA-1, BCL2 |
MiR-200
| BrC, PDA, GC, HNSCC, M, OC, PC | FN1, MSN, NTRK2, LEPR, ARHGAP19, ZEB1/2, Flt1/VEGFR1, FAP-1, FOG2, ERRFI-1 |
MiR-205
| M, BrC, PC, ESCC, HNSCC | Runx2, E2F1, ErbB3, Zeb1 |
MiR-31
| PTC, CRC, BrC, LC, GC, HCC | LATS2, WAVE3, SATB2, ITGA5, RDX, RhoA, FIH |
MiR-126
| CRC, GC, BrC, SCLC, AML, NSCLC, HCC | SLC7A5, SOX2, PLAC1, VEGFA, PIK3R2, Crk, EGFL7, p85beta |
MiR-210
| PDA, RCC, BrC, PC, GBM, NSCLC, OC, GC, HNSCC | FGFRL1, SDHD, MNT |
MiR-9
| GBM, PC, nHL, EC, OC | CAMTA1, PDGFR-β, CDX2, PRDM-1, E-cadherin, NF-kappaB1 |
MiR-141
| PC, EC, CRC, HNSCC, LC, BrC, ESCC, OC, RCC | SIP1, YAP1 |
MiR-122
| HCC, RCC | Bcl-w, ADAM17 |
Small interfering RNAs
Gene target | Drug type | Drug name | Clinical phase | Notes |
---|---|---|---|---|
Bcl-2 | LNA-oligo | SPC2996 | I/II | CLL |
Immunoproteasome β-subunits LMP2, LMP7 and MECL1 | siRNA | Proteasome siRNA | I | Metastatic lymphoma |
PLK1 | siRNA | PLK SNALP | pre-clinical | |
M2 subunit of ribonucleotide reductase | siRNA | CALAA-01 | I | Solid tumors |
PKN3 | siRNA | Atu027 | I | Solid tumors |
KSP and VEGF | siRNA | ALN-VSP | I | Solid tumors |
Survivin | LNA-oligo | EZN3042 | I/II | Solid tumors |
HIF-1α | LNA-oligo | EZN2968 | I/II | Solid tumors |
Furin | shRNA | FANG vaccine | I | Solid tumors |
eiF-4E | LNA-oligo | elF-4E ASO | I | Solid tumors |
Survivin | LNA-oligo | Survivin ASO | II | Solid tumors |
Piwi proteins associated RNAs
Small nucleolar RNAs
Promoter-associated RNAs
Centromere repeat associated small interacting RNAs
Telomere-specific small RNAs
Pyknons
Long non-coding RNAs
LncRNA | Size | Cytoband | Cancer types | References |
---|---|---|---|---|
HOTAIR
| 2158 nt | 12q13.13 | breast | |
MALAT1/α/NEAT2
| 7.5 kb | 11q13.1 | breast, lung, uterus, pancreas, colon, prostate, liver, osteosarcoma, neuroblastoma, cervix | |
HULC
| 500 nt | 6p24.3 | liver | |
BC200
| 200 nt | 2p21 | breast, cervix, esophagus, lung, ovary, parotid, tongue | |
H19
| 2.3 kb | 11p15.5 | bladder, lung, liver, breast, endometrial, cervix esophagus, ovary, prostate, colorectal | |
BIC/MIRHG155/MIRHG2
| 1.6 kb | 21q11.2 | B-cell lymphoma | [160] |
PRNCR1
| 13 kb | 8q24.2 | prostate | [161] |
LOC285194
| 2105 nt | 3q13.31 | osteosarcoma | [162] |
PCGEM1
| 1643 nt | 2 g32.2 | prostate | |
UCA1/CUDR
| 1.4–2.7 kb | 19p13.12 | bladder, colon, cervix, lung, thyroid, liver, breast, esophagus, stomach | [166] |
DD3/PCA3
| 0.6–4 kb | 9q21.22 | prostate | |
anti-NOS2A
| 1.9 kb | 17q23.2 | brain | [169] |
uc.73A
| 201 nt | 2q22.3 | colon | [170] |
uc.338
| 590 nt | 12q13.13 | liver | [171] |
ANRIL/p15AS/CDK2BAS
| 34.8 kb | 9p21.3 | prostate, leukemia | |
MEG3
| 1.6 kb | 14q32.2 | brain | |
GAS5/SNHG2
| isoforms | 1q25.1 | breast | [101] |
SRA-1/SRA
| 1965 nt | 5q31.3 | breast, uterus, ovary | |
PTENP1
| 3.9 kb | 9p13.3 | prostate | |
ncRAN
| 2186 nt 2087 nt | 17q25.1 | bladder, neuroblastoma | |
LSINCT5
| 2.6 kb | 5p15.33 | breast, ovary | [185] |