Supplementary table S1: ncRNA databases
Database / ncRNA species / Description / URL / ReferencesNONCODE / ncRNA / Database for almost all types of ncRNA (except tRNA and rRNA), including information on sequences and cellular functions. / / Liu, 2005
RNAcentral / ncRNA / Comprehensive ncRNA sequence database formed by consolidating information from 42 specialized ncRNA resources. / rnacentral.org / The RNAcentral consortium, 2017
miRBase / miRNA / Primary miRNA sequence repository. / / Kozomara and Griffiths-Jones, 2013
TargetScan / miRNA / Predicts biological targets of miRNA through presence of conserved sites in the 3’UTR that match the miRNA seed region. / / Agarwal, 2015
PicTar / miRNA / Predicts biological targets of miRNA through presence of miRNA seed matches in the 3’UTR. / / (Krek et al., 2005)
rna22 / miRNA / miRNA target prediction through analysis of miRNA seed matches present in the 3’UTR, 5’UTR and CDS based on the Teiresias algorithm. / https://cm.jefferson.edu/rna22/ / Loher, 2012
PITA / miRNA / miRNA target prediction algorithm based on secondary structures predicted to form in the 3’UTR. / / (Kertesz et al., 2007)
miRDB / miRNA / miRNA target prediction through miRNA seed matches in the 3’UTR, 5’UTR and CDS. Also includes functional annotations of miRNA. / / (Wong and Wang, 2015)
microRNA.org/Miranda / miRNA / miRNA target prediction using the miRanda algorithm, which is based on sequence complementarity between seed matches in the 3’UTR and free energy of the duplex. / / (Betel et al., 2010)
DIANA-microT-CDS / miRNA / miRNA target prediction based on bioinformatics and experimental approaches to determine the important rules in miRNA seed recognition in the 3’UTR and CDS regions. / / (Kiriakidou et al., 2004)
lncrnadb / lncRNA / Reference database for functional lncRNA. / / Amaral, 2011
LNCipedia / lncRNA / Database of annotated lncRNA transcripts, including information on structure, protein coding potential and microRNA binding sites. / / (Volders et al., 2013)
CHIPBase / lncRNA / Database for studying the expression and transcriptional regulatory networks of ncRNA / rna.sysu.edu.cn/chipbase / (Zhou et al., 2017)
DIANA-LncBase / lncRNA / Database provides comprehensive annotation of miRNA targets on lncRNA, which have either been experimentally verified or computationally predicted. / / (Paraskevopoulou et al., 2013)
circBase / circRNA / Database containing circRNA that have been identified through various screens and evidence supporting their expression can be accessed and downloaded. / / Glazar, 2014
circRNADb / circRNA / Database containing genomic sequence, IRES and open reading frame information. / www.reprod.njmu.edu.cn/circrnadb/ / (Chen et al., 2016)
Supplementary table S2: Selected ncRNAs in the NF-κB pathway.
ncRNA / Model System / Phenotype / Targets / ReferencemiR-155 / Macrophages (RAW264.7) stimulated with LPS / LPS stimulation resulted in the upregulation of miR-155.
E-miR-155 transgenic mice produced higher levels of TNF-when exposed to LPS, and were sensitive to septic shock. / IB / Tili et al. 2007
miR-146 / LPS-stimulated THP1 cells, mir146a KO mice / miR-146a controls cytokine signalling downstream of Toll-like receptor. mir146a KO mice show myeloid malignancies / IRAK1, TRAF6 / Taganov et al., 2006
Lethe / Wild type mouse embryonic fibroblast stimulated with TNF-α / Induced by proinflammatory cytokines and glucocorticoid receptor agonist and act as negative feed-back regulator of NF-κB and its level decreases with aging / RelA (p65) / Rapicavoli et al. 2013
NKILA / MDA-MB-231 breast cancer cells stimulated with TNF-α, IL1-β, or LPs / NKILA is induced by NF-κB signalling acts as a negative regulator of NF-κB by blocking IκB phosphorylation / NF-κB/IκB / Liu et al., 2015
PACER / Human mammary epithelial cells and monocyte/macrophage cell lines / Pacer is induced upon expression of Cox2, and interacts with the p50 inhibitory subunit of NF-B. / p50 / Krawcyzk et al., 2014
lincRNA-Tnfaip3 / Macrophages (RAW264.7) stimulated with LPS / Expression is induced upon NF-B activation, required for transactivation of NF-B regulated inflammatory genes / NF-B and Hmgb1 complex / Ma et al., 2017
lincRNA-Cox2 / Macrophages stimulated with synthetic bacterial lipopeptide, Pam3CSK4, a TLR2 ligand / Expression of lincRNA-Cox2 is dependent on MyD88 and NF-B.
Interacts with hnRNP-A/B to repress transcription of a subset of immune genes.
Also found to activate late NF-B response genes. / hnRNP-A/B
SWI/SNF / Carpenter et al., 2013
Hu et al., 2016
lincRNA-EPS / TLR2 activated bone marrow derived macrophages
lincRNA-EPS KO mice / lincRNA-EPS is expressed in basal level in macrophages and represses expression of immune regulatory genes via regulating nucleosome positioning in target genes. / hnRNPL / Atianand et al., 2016
THRIL / THP1-derived macrophages stimulated with Pam3CSK4 / Regulates expression of many immune-related genes and THRIL expression is increases in Kawasaki patients / hnRNPL / Li et al., 2014
mcircRasGEF1B / Mouse macrophage cells induced with lipid A / Regulates the stability of ICAM-1 mature mRNA / Unknown mechanism / Ng et al., 2016
Supplementary table S3: Selected ncRNAs in the JAK/STAT and MAPK pathways.
ncRNA / Model System / Phenotype / Targets / ReferenceJAK/STAT
miR-135 / Primary gastric cancer tissues / Downregulated in gastric tumours, when compared with adjacent non-tumour tissues / JAK2 / Wu et al., 2012
miR-145 / Colon cancer cell line and non-tumorigenic cell lines / Downregulated in all tested cancer cell lines. Overexpression reduced proliferative potential of DLD-1 cells / STAT1 / Gregersen et al., 2010
miR-145 / T cells derived from five SLE patients and 5 healthy controls / Downregulated in SLE T cells, STAT1 mRNA overexpressed / STAT1 / Lu et al., 2013
miR221/222 / Knockdown of miR-221/222 in U251 glioma cells, look at differential gene expression by microarray / Knockdown of miR221/222 increased STAT1/2 expression and phosphorylation. / STAT1/2 / Zhang et al., 2010
miR-124 / Colon tissues of paediatric patients / Elevated levels of phospho-STAT3 in UC tissues; overexpression of miR-124 decreased phosphor-STAT3 levels; mice with experimental colitis displayed inverse correlation of miR-124 and STAT3 levels / STAT3 / Koukos et al., 2013
Let-7 / miRNA microarray to compare miRNA expression in Hepatitis B virus x protein (HBx) HepG2 cells versus control HepG2 cells / HBx decreases let-7 levels, resulting in increases STAT3 expression and consequent cell proliferation in HBx cells. / STAT3 / Wang et al., 2010
lncRNA HOXD-AS1 / Microarray data from NB patient tumour samples / Increase transcription of JAK/STAT target genes / Yarmishyn et al., 2014
lncRNA-CMPK2 / High-throughput RNA-seq on IFN- stimulated human primary hepatocytes / Expression dependent on JAK/STAT signalling, negatively regulates IFN response; knockdown results in marked reduction of HCV replication / Kambara et al., 2014
ANRIL / Patient samples / Expression is dependent on JAK/STAT pathway / Aguilo et al., 2016 Helgadottir et al., 2008
OLA1P2 / Colorectal carcinoma cells were treated with aspirin, and microarray analysis performed. / Upregulated upon treatment with aspirin.
Inhibits nuclear import of phosphorylated STAT3 by binding to and preventing homodimerization of phosphorylated STAT3. / STAT3 / Guo et al., 2016
lnc-DC / Human dendritic cells and mouse bone marrow cells / Induced upon human dendritic cell differentiation.
Associates with STAT3 to prevent dephosphorylation by SHP1. / STAT3 / Wang et al., 2014
MAPK
miR-125a-3p / Animal model of orofacial inflammatory pain and behavioural tests in Sprague-dawley rats / miR-125a-3p downregulated upon induction of inflammation / p38 / Dong et al., 2014
miR125b / Human cell lines and tissue samples of malignant melanoma and melanocytes / miR-125b expression significantly reduced in malignant melanoma / JNK / Kappelmann et al., 2013
miR216b / NIH3T3 cells challenged with tunicamycin / Induction of CHOP/GADD153 increases miR-216b expression, which then targets JNK, sensitizing cells to ER stress-dependent apoptosis. / JNK / Xu et al., 2016
MALAT1 / STZ-induced diabetic rates and db/db mice / Expression is upregulated in retinas of diabetic rats / mice. Implicated in diabetes-induced microvascular dysfunction. / Crosstalk with p38 signalling involved in regulation of endothelial cell function / Liu et al., 2014
lncRNA BANCR / Lung carcinoma tissues and cell lines / BANCR downregulated in LC tissues and cell lines. Overexpression suppressed tumour growth, knockdown promoted cell proliferation and migration of LC. / Suppress both p38 and JNK activation / Jiang et al. 2014
NEAT1 / Cell lines transfected with poly I:C / Expressed upon poly I:C induced activation of p38, induces expression of antiviral cytokines and IL-8 / Relocation of SFPQ from IL8 promoter to paraspeckles / Imamura et al., 2014
Supplementary References:
Betel, D., Koppal, A., Agius, P., Sander, C., and Leslie, C. (2010). Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 11, R90.
Chen, X., Han, P., Zhou, T., Guo, X., Song, X., and Li, Y. (2016). circRNADb: A comprehensive database for human circular RNAs with protein-coding annotations. Sci Rep 6, 34985.
Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., and Segal, E. (2007). The role of site accessibility in microRNA target recognition. Nat Genet 39, 1278-1284.
Kiriakidou, M., Nelson, P.T., Kouranov, A., Fitziev, P., Bouyioukos, C., Mourelatos, Z., and Hatzigeorgiou, A. (2004). A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18, 1165-1178.
Krek, A., Grun, D., Poy, M.N., Wolf, R., Rosenberg, L., Epstein, E.J., MacMenamin, P., da Piedade, I., Gunsalus, K.C., Stoffel, M., et al. (2005). Combinatorial microRNA target predictions. Nat Genet 37, 495-500.
Paraskevopoulou, M.D., Georgakilas, G., Kostoulas, N., Reczko, M., Maragkakis, M., Dalamagas, T.M., and Hatzigeorgiou, A.G. (2013). DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs. Nucleic Acids Res 41, D239-245.
Volders, P.J., Helsens, K., Wang, X., Menten, B., Martens, L., Gevaert, K., Vandesompele, J., and Mestdagh, P. (2013). LNCipedia: a database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res 41, D246-251.
Wong, N., and Wang, X. (2015). miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43, D146-152.
Zhou, K.R., Liu, S., Sun, W.J., Zheng, L.L., Zhou, H., Yang, J.H., and Qu, L.H. (2017). ChIPBase v2.0: decoding transcriptional regulatory networks of non-coding RNAs and protein-coding genes from ChIP-seq data. Nucleic Acids Res 45, D43-D50.