762
Views
0
CrossRef citations to date
0
Altmetric
Review

Non-coding 886 (nc886/vtRNA2-1), the epigenetic odd duck – implications for future studies

ORCID Icon, ORCID Icon & ORCID Icon
Article: 2332819 | Received 08 Dec 2023, Accepted 14 Mar 2024, Published online: 25 Mar 2024

References

  • Marttila S, Viiri LE, Mishra PP. et al. Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs. Clin Epigenetics 2021;13(1). doi: 10.1186/s13148-021-01132-3
  • Zink F, et al. Insights into imprinting from parent-of-origin phased methylomes and transcriptomes. Nature Genet. 2018;50(11):1542–20. doi: 10.1038/s41588-018-0232-7
  • Dugué PA, Yu C, McKay T, et al. vtRNA2‐1: genetic variation, heritable methylation and disease association. Int J Mol Sci. 2021;22(5):1–18. doi: 10.3390/ijms22052535
  • Dowty JG, et al. Heritable methylation marks associated with prostate cancer risk. Fam Cancer. 2023;22(3):313–317. doi: 10.1007/s10689-022-00325-w
  • Dugué PA, et al. Heritable methylation marks associated with breast and prostate cancer risk. Prostate. 2018;78(13):962–969. doi: 10.1002/pros.23654
  • Marttila S, et al. Methylation status of vtRNA2-1/nc886 is stable across human populations, monozygotic twin pairs and in majority of somatic tissues. 2022. doi: 10.1101/2022.06.21.496995
  • Carpenter BL, et al. Mother–child transmission of epigenetic information by tunable polymorphic imprinting. Proc Natl Acad Sci, USA. 2018;115(51). doi: 10.1073/pnas.1815005115
  • Carpenter BL, et al. Oocyte age and preconceptual alcohol use are highly correlated with epigenetic imprinting of a noncoding RNA (nc886). Proc Natl Acad Sci, USA. 2021;118(12). doi: 10.1073/pnas.2026580118
  • Fort RS, Garat B, Sotelo-Silveira JR, et al. vtRNA2-1/nc886 produces a small RNA that contributes to its tumor suppression action through the microRNA pathway in prostate cancer. Noncoding RNA. 2020;6(1):7. doi: 10.3390/ncrna6010007
  • Lee YS. Are we studying non-coding RNAs correctly? Lessons from nc886. Int J Mol Sci. 2022;23(8):4251. doi: 10.3390/ijms23084251
  • Treppendahl MB, Qiu X, Søgaard A, et al. Allelic methylation levels of the noncoding vtRNA2-1 located on chromosome 5q31.1 predict outcome in AML. Blood. 2012;119(1):206–216. doi: 10.1182/blood-2011-06-362541
  • Park J-L, Lee Y-S, Song M-J, et al. Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis. Oncogene. 2017;36(49):6793–6804. doi: 10.1038/onc.2017.285
  • Silver MJ, et al. Independent genomewide screens identify the tumor suppressor vtRNA2-1 as a human epiallele responsive to periconceptional environment. Genome Bio. 2015;16(1). doi: 10.1186/s13059-015-0660-y
  • Finer S, Iqbal MS, Lowe R, et al. Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study. BMJ Open. 2016;6(11):e011768. doi: 10.1136/bmjopen-2016-011768
  • Lee Y-S, Lee YS. nc886, an RNA polymerase III-Transcribed noncoding RNA whose expression is dynamic and regulated by intriguing mechanisms. Int J Mol Sci. 2023;24(10):8533. doi: 10.3390/ijms24108533
  • Minones-Moyano E, Friedländer MR, Pallares J, et al. Upregulation of a small vault RNA (vtRNA2-1a) is an early event in Parkinson disease and induces neuronal dysfunction. RNA Biol. 2013;10(7):1093–1106. doi: 10.4161/rna.24813
  • Barker DJP, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in england and WALES. Lancet. 1986;327(8489):1077–1081. doi: 10.1016/S0140-6736(86)91340-1
  • Landgraf P, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129(7):1401–1414. doi: 10.1016/j.cell.2007.04.040
  • Yue J, Sheng Y, Orwig KE. Identification of novel homologous microRNA genes in the rhesus macaque genome. BMC Genomics. 2008;9(1):8. doi: 10.1186/1471-2164-9-8
  • Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation. RNA. 2003;9(3):277–279. doi: 10.1261/rna.2183803
  • Stadler PF, et al. Evolution of vault RNAs. Mol Biol Evol. 2009;26(9):1975–1991. doi: 10.1093/molbev/msp112
  • Nandy C, Mrázek J, Stoiber H, et al. Epstein–barr virus-induced expression of a novel human vault RNA. J Mol Biol. 2009;388(4):776–784. doi: 10.1016/j.jmb.2009.03.031
  • Mrázek J, Kreutmayer SB, Grässer FA, et al. Subtractive hybridization identifies novel differentially expressed ncRNA species in EBV-infected human B cells. Nucleic Acids Res. 2007;35(10):e73. doi: 10.1093/nar/gkm244
  • Gallo S, Kong E, Ferro I, et al. Small but powerful: the human vault RNAs as multifaceted modulators of pro-survival characteristics and tumorigenesis. Cancers (Basel). 2022;14(11):2787. doi: 10.3390/cancers14112787
  • Lee K, et al. Precursor miR-886, a novel noncoding RNA repressed in cancer, associates with PKR and modulates its activity. RNA. 2011;17(6):1076–1089. doi: 10.1261/rna.2701111
  • Canella D, Praz V, Reina JH, et al. Defining the RNA polymerase III transcriptome: genome-wide localization of the RNA polymerase III transcription machinery in human cells. Genome Res. 2010;20(6):710–721. doi: 10.1101/gr.101337.109
  • Kostiniuk D, Tamminen H, Mishra PP, et al. Methylation pattern of polymorphically imprinted nc886 is not conserved across mammalia. PloS One. 2022;17(3):e0261481. doi: 10.1371/journal.pone.0261481
  • Kunkeaw N, Lee Y-S, Im WR, et al. Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound. Proc Natl Acad Sci USA. 2019;116(17):8289–8294. doi: 10.1073/pnas.1814510116
  • Ahn J-H, Lee H-S, Lee J-S, et al. nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer. Nat Commun. 2018;9(1):1166. doi: 10.1038/s41467-018-03556-7
  • Kunkeaw N, Jeon SH, Lee K, et al. Cell death/proliferation roles for nc886, a non-coding RNA, in the protein kinase R pathway in cholangiocarcinoma. Oncogene. 2013;32(32):3722–3731. doi: 10.1038/onc.2012.382
  • Calderon BM, Conn GL. Human noncoding RNA 886 (nc886) adopts two structurally distinct conformers that are functionally opposing regulators of PKR. RNA. 2017;23(4):557–566. doi: 10.1261/rna.060269.116
  • Calderon BM, Conn GL. A human cellular noncoding RNA activates the antiviral protein 2′–5′-oligoadenylate synthetase 1. J Biol Chem. 2018;293(41):16115–16124. doi: 10.1074/jbc.RA118.004747
  • Lee YS. A novel type of non-coding RNA, nc886, implicated in tumor sensing and suppression. Genomics Inform. 2015;13(2):26. doi: 10.5808/gi.2015.13.2.26
  • Sharbati J, et al. Integrated microRNA-mRNA-analysis of human monocyte derived macrophages upon mycobacterium avium subsp. hominissuis infection. PLoS One. 2011;6(5):e20258. doi: 10.1371/journal.pone.0020258
  • Saruuldalai E, Park J, Kang D, et al. A host non-coding RNA, nc886, plays a pro-viral role by promoting virus trafficking to the nucleus. Mol Ther Oncolytics. 2022;24:683–694. doi: 10.1016/j.omto.2022.02.018
  • Lee Y-S, Bao X, Lee H-H, et al. Nc886, a novel suppressor of the type I interferon response upon pathogen intrusion. Int J Mol Sci. 2021;22(4):2003. doi: 10.3390/ijms22042003
  • Fort RS, Duhagon MA. Pan-cancer chromatin analysis of the human vtRNA genes uncovers their association with cancer Biology. 2021. doi: 10.12688/f1000research.28510.2
  • Yu S, et al. Microarray analysis of differentially expressed microRnas in allergic rhinitis. Am J Rhinol Allergy. 2011. doi: 10.2500/ajra.2011.25.3682
  • Suojalehto H, Lindström I, Majuri M-L, et al. Altered microRNA expression of nasal mucosa in long-term asthma and allergic rhinitis. Int Arch Allergy Immunol. 2014;163(3):168–178. doi: 10.1159/000358486
  • Lee K-S, Cho E, Weon JB, et al. Inhibition of UVB-Induced inflammation by laminaria japonica extract via regulation of nc886-PKR pathway. Nutrients. 2020;12(7):1958. doi: 10.3390/nu12071958
  • Lee K-S, Shin S, Cho E, et al. nc886, a non-coding RNA, inhibits UVB-induced MMP-9 and COX-2 expression via the PKR pathway in human keratinocytes. Biochem Biophys Res Commun. 2019;512(4):647–652. doi: 10.1016/j.bbrc.2019.01.068
  • Joo JE, et al. Heritable DNA methylation marks associated with susceptibility to breast cancer. Nat Commun 2018;9(1). doi: 10.1038/s41467-018-03058-6
  • Romanelli V, et al. Variable maternal methylation overlapping the nc886/vtRNA2-1 locus is locked between hypermethylated repeats and is frequently altered in cancer. Epigenetics. 2014;9(5):783–790. doi: 10.4161/epi.28323
  • Hu Z, Zhang H, Tang L, et al. Silencing nc886, a non-coding RNA, induces apoptosis of human endometrial cancer cells-1A in vitro. Med Sci Monit. 2017;23:1317–1324. doi: 10.12659/MSM.900320
  • Ross JP, van Dijk S, Phang M, et al. Batch-effect detection, correction and characterisation in Illumina HumanMethylation450 and MethylationEPIC BeadChip array data. Clin Epigenetics. 2022;14(1):58. doi: 10.1186/s13148-022-01277-9
  • Lewis A, Reik W. How imprinting centres work. Cytogenet Genome Res. 2006;113(1–4):81–89. doi: 10.1159/000090818
  • Pervjakova N, Kasela S, Morris AP, et al. Imprinted genes and imprinting control regions show predominant intermediate methylation in adult somatic tissues. Epigenomics. 2016;8(6):789–799. doi: 10.2217/epi.16.8
  • Monk D. Germline-derived DNA methylation and early embryo epigenetic reprogramming: the selected survival of imprints. Int J Biochem Cell Biol. 2015;67:128–138. doi: 10.1016/j.biocel.2015.04.014
  • Baran Y, Subramaniam M, Biton A, et al. The landscape of genomic imprinting across diverse adult human tissues. Genome Res. 2015;25(7):927–936. doi: 10.1101/gr.192278.115
  • Sanchez-Delgado M, Court F, Vidal E, et al. Human oocyte-derived methylation differences persist in the placenta revealing widespread transient imprinting. PloS Genet. 2016;12(11):e1006427. doi: 10.1371/journal.pgen.1006427
  • Carli D, Riberi E, Ferrero GB, et al. Syndromic disorders caused by disturbed human imprinting. J Clin Res Pediatr Endocrinol. 2020;12(1):1–16. doi: 10.4274/jcrpe.galenos.2019.2018.0249
  • Olsen KW, Castillo-Fernandez J, Zedeler A, et al. A distinctive epigenetic ageing profile in human granulosa cells. Hum Reprod. 2020;35(6):1332–1345. doi: 10.1093/humrep/deaa071
  • Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 2012;13(7):484–492. doi: 10.1038/nrg3230
  • Lee H-S, Lee K, Jang H-J, et al. Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis. Oncotarget. 2014;5(11):3472–3481. doi: 10.18632/oncotarget.1927
  • Lee K-S, Park J-L, Lee K, et al. nc886, a non-coding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. Oncotarget. 2014;5(11):3944–3955. doi: 10.18632/oncotarget.2047
  • Sallustio F, Serino G, Cox S, et al. Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy. Clin Sci. 2016;130(9):733–746. doi: 10.1042/CS20150711
  • Court F, Tayama C, Romanelli V, et al. Genome-wide parent-of-origin DNA methylation analysis reveals the intricacies of human imprinting and suggests a germline methylation-independent mechanism of establishment. Genome Res. 2014;24(4):554–569. doi: 10.1101/gr.164913.113
  • Okae H, Chiba H, Hiura H, et al. Genome-wide analysis of DNA methylation dynamics during early human development. PloS Genet. 2014;10(12):e1004868. doi: 10.1371/journal.pgen.1004868
  • Jima DD, Skaar DA, Planchart A, et al. Genomic map of candidate human imprint control regions: the imprintome. Epigenetics. 2022;17(13):1920–1943. doi: 10.1080/15592294.2022.2091815
  • Zhu P, Guo H, Ren Y, et al. Single-cell DNA methylome sequencing of human preimplantation embryos. Nat Genet. 2018;50(1):12–19. doi: 10.1038/s41588-017-0007-6
  • Obata Y, Kono T. Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth*. J Biol Chem. 2002;277(7):5285–5289. doi: 10.1074/jbc.M108586200
  • Guo H, Zhu P, Yan L, et al. The DNA methylation landscape of human early embryos. Nature. 2014;511(7511):606–610. doi: 10.1038/nature13544
  • You Y-A, Kwon EJ, Hwang H-S, et al. Elevated methylation of the vault RNA2-1 promoter in maternal blood is associated with preterm birth. BMC Genomics. 2021;22(1):528. doi: 10.1186/s12864-021-07865-y
  • Gopalan S, Carja O, Fagny M, et al. Trends in DNA methylation with age replicate across diverse human populations. Genetics. 2017;206(3):1659–1674. doi: 10.1534/genetics.116.195594
  • Heyn H, Moran S, Hernando-Herraez I, et al. DNA methylation contributes to natural human variation. Genome Res. 2013;23(9):1363–1372. doi: 10.1101/gr.154187.112
  • Fagny M, Patin E, MacIsaac JL, et al. The epigenomic landscape of African rainforest hunter-gatherers and farmers. Nat Commun. 2015;6(1):10047. doi: 10.1038/ncomms10047
  • Natri HM, Bobowik KS, Kusuma P, et al. Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago. PLoS Genet. 2020;16(5):e1008749. doi: 10.1371/journal.pgen.1008749
  • Sirugo G, Williams SM, Tishkoff SA. The missing diversity in human genetic studies. Cell. 2019;177(1):26–31. doi: 10.1016/j.cell.2019.02.048
  • Markunas CA, et al. Maternal age at delivery is associated with an epigenetic signature in both newborns and adults. PLoS One. 2016;11(7):e0156361. doi: 10.1371/journal.pone.0156361
  • Richmond RC, Sharp GC, Herbert G, et al. The long-term impact of folic acid in pregnancy on offspring DNA methylation: follow-up of the aberdeen folic acid supplementation trial (AFAST). Int J Epidemiol. 2018;47(3):928–937. doi: 10.1093/ije/dyy032
  • Van Der Plaat DA, et al. Occupational exposure to pesticides is associated with differential DNA methylation. Occup Environ Med. 2018;75(6):427–435. doi: 10.1136/oemed-2017-104787
  • van der Plaat DA, Vonk JM, Terzikhan N, et al. Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression. Hum Mol Genet. 2019;28(15):2477–2485. doi: 10.1093/hmg/ddz067
  • Ambatipudi S, Cuenin C, Hernandez-Vargas H, et al. Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study. Epigenomics. 2016;8(5):599–618. doi: 10.2217/epi-2016-0001
  • Xu R, Li S, Wu Y, et al. Wildfire-related PM2.5 and DNA methylation: an Australian twin and family study. Environ Int. 2023;171:107704. doi: 10.1016/j.envint.2022.107704
  • Eze IC, Jeong A, Schaffner E, et al. Genome-wide DNA methylation in peripheral blood and long-term exposure to source-specific transportation noise and air pollution: the SAPALDIA study. Environ Health Perspect. 2020;128(6):067003. doi: 10.1289/EHP6174
  • Tobi EW, Goeman JJ, Monajemi R, et al. DNA methylation signatures link prenatal famine exposure to growth and metabolism. Nat Commun. 2014;5(1):5592. doi: 10.1038/ncomms6592
  • Peter CJ, Fischer LK, Kundakovic M, et al. DNA methylation signatures of early childhood malnutrition associated with impairments in attention and cognition. Biological Psychiatry. 2016;80(10):765–774. doi: 10.1016/j.biopsych.2016.03.2100
  • Boks MP, Houtepen LC, Xu Z, et al. Genetic vulnerability to DUSP22 promoter hypermethylation is involved in the relation between in utero famine exposure and schizophrenia. NPJ Schizophr. 2018;4(1):1–8. doi: 10.1038/s41537-018-0058-4
  • Van Dijk SJ, Peters TJ, Buckley M, et al. DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood. Int J Obesity. 2018;42(1):28–35. doi: 10.1038/ijo.2017.228
  • Gonseth S, Shaw GM, Roy R, et al. Epigenomic profiling of newborns with isolated orofacial clefts reveals widespread DNA methylation changes and implicates metastable epiallele regions in disease risk. Epigenetics. 2019;14(2):198–213. doi: 10.1080/15592294.2019.1581591
  • Henderson AR, Wang Q, Meechoovet B, et al. DNA methylation and expression profiles of whole blood in Parkinson’s disease. Front Genet. 2021;12. doi: 10.3389/fgene.2021.640266
  • Chuang YH, Paul KC, Bronstein JM, et al. Parkinson’s disease is associated with DNA methylation levels in human blood and saliva. Genome Med. 2017;9(1). doi: 10.1186/s13073-017-0466-5
  • Vallerga CL, Zhang F, Fowdar J, et al. Analysis of DNA methylation associates the cystine–glutamate antiporter SLC7A11 with risk of Parkinson’s disease. Nat Commun. 2020;11(1):1238. doi: 10.1038/s41467-020-15065-7
  • Sallustio F, Picerno A, Cimmarusti MT, et al. Elevated levels of IL-6 in IgA nephropathy patients are induced by an epigenetically driven mechanism modulated by viral and bacterial RNA. Eur J Internal Med. 2023;118:108–117. doi: 10.1016/j.ejim.2023.07.045
  • Li JH, Xiao X, Zhang Y-N, et al. MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells. Gynecol Oncol. 2011;120(1):145–151. doi: 10.1016/j.ygyno.2010.09.009
  • Kong L, Hao Q, Wang Y, et al. Regulation of p53 expression and apoptosis by vault RNA2-1-5p in cervical cancer cells. Oncotarget. 2015;6(29):28371–28388. doi: 10.18632/oncotarget.4948
  • Li J-H, Wang M, Zhang R, et al. E2F1-directed activation of nc886 mediates drug resistance in cervical cancer cells via regulation of major vault protein. Int J Clin Exp Pathol. 2017;10(9):9233–9242.
  • Zhang L-L, Wu J, Liu Q, et al. MiR-886-5p inhibition inhibits growth and induces apoptosis of MCF7 cells. Asian Pac J Cancer Prev. 2014;15(4):1511–1515. doi: 10.7314/APJCP.2014.15.4.1511
  • Khoshnevisan A, Parvin M, Ghorbanmehr N, et al. A significant upregulation of miR-886-5p in high grade and invasive bladder tumors. Urol J. 2015;12(3):2160–2164.
  • McDonald AC, Vira M, Walter V, et al. Circulating microRnas in plasma among men with low-grade and high-grade prostate cancer at prostate biopsy. Prostate. 2019;79(9):961–968. doi: 10.1002/pros.23803
  • Pan B, Yu J, Liu X. Upregulation of miR-886 indicates poor prognosis and promotes tumour progression of prostate cancer. Andrologia. 2022;54(1):e14296. doi: 10.1111/and.14296
  • Xiang P, Liu Y, Liu L, et al. The biological function and clinical significance of miR-886-5p in multiple myeloma. AHA. 2019;142(4):208–216. doi: 10.1159/000499620
  • Lei J, Xiao J-H, Zhang S-H, et al. Non-coding RNA 886 promotes renal cell carcinoma growth and metastasis through the janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. Mol Med Rep. 2017;16(4):4273–4278. doi: 10.3892/mmr.2017.7093
  • Jang H-J, Lee H-S, Burt BM, et al. Integrated genomic analysis of recurrence-associated small non-coding RNAs in oesophageal cancer. Gut. 2017;66(2):215–225. doi: 10.1136/gutjnl-2015-311238
  • Fort RS, Mathó C, Geraldo MV, et al. Nc886 is epigenetically repressed in prostate cancer and acts as a tumor suppressor through the inhibition of cell growth. BMC Cancer 2018;18(1). doi: 10.1186/s12885-018-4049-7
  • Yang R, Zuo L, Ma H, et al. Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT. Genes Dis. 2022;9(4):1086–1098. doi: 10.1016/j.gendis.2020.12.010
  • Liang S, et al. Screening and identification of potential miRNA involved in ovarian cancer invasion and metastasis. Zhonghua Zhong Liu Za Zhi. 2010;32(9):650–654.
  • Tahiri A, Leivonen S-K, Lüders T, et al. Deregulation of cancer-related miRnas is a common event in both benign and malignant human breast tumors. Carcinogenesis. 2014;35(1):76–85. doi: 10.1093/carcin/bgt333
  • Xiong Y, et al. MiR-886-3p regulates cell proliferation and migration, and is dysregulated in familial non-medullary thyroid cancer. PLoS One. 2011;6(10):e24717. doi: 10.1371/journal.pone.0024717
  • Dettmer MS, et al. MicroRNA profile of poorly differentiated thyroid carcinomas – new diagnostic and prognostic insights. J Mol Endocrinol. 2014;52(2):181–189. doi: 10.1530/JME-13-0266
  • Bi N, Cao J, Song Y, et al. A microRNA signature predicts survival in early stage small-cell lung cancer treated with surgery and adjuvant chemotherapy. PLoS One. 2014;9(3):e91388. doi: 10.1371/journal.pone.0091388
  • Gao W, Shen H, Liu L, et al. MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. J Cancer Res Clin Oncol. 2011;137(4):557–566. doi: 10.1007/s00432-010-0918-4
  • Zhang Y, Wang X, Han S, et al. Suppression of mir-886-3P mediated by Arecoline (are) contributes to the progression of oral squamous cell carcinoma. J Invest Med. 2021;69(2):377–381. doi: 10.1136/jim-2020-001405
  • Xu Y, Wang Z, Wei P, et al. Hypermethylation of nc886 in HPV-positive oropharyngeal cancer and its clinical implications: an epigenome-wide association study. Mol Ther Nucleic Acids. 2022;30:596–605. doi: 10.1016/j.omtn.2022.11.012
  • Im WR, Lee H-S, Lee Y-S, et al. A regulatory noncoding RNA, nc886, suppresses esophageal cancer by inhibiting the AKT pathway and cell cycle progression. Cells. 2020;9(4):801. doi: 10.3390/cells9040801
  • Gao W, Zhang S, Guorong L, et al. Nc886 promotes renal cancer cell drug-resistance by enhancing EMT through Rock2 phosphorylation-mediated β-catenin nuclear translocation. Cell Cycle. 2022;21(4):340–351. doi: 10.1080/15384101.2021.2020431
  • Nordentoft I, Birkenkamp-Demtroder K, Agerbæk M, et al. miRnas associated with chemo-sensitivity in cell lines and in advanced bladder cancer. BMC Med Genomics. 2012;5(1):40. doi: 10.1186/1755-8794-5-40
  • Cao J, et al. DNA methylation-mediated repression of miR-886-3p predicts poor outcome of human small cell lung cancer. Cancer Res. 2013;73(11):3326–3335. doi: 10.1158/0008-5472.CAN-12-3055
  • Shen J, Zhou W, Bi N, et al. MicroRNA-886-3P functions as a tumor suppressor in small cell lung cancer. Cancer Biol Ther. 2018;19(12):1185–1192. doi: 10.1080/15384047.2018.1491505
  • Schou JV, Rossi S, Jensen BV, et al. miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and Irinotecan. PLoS One. 2014;9(6):e99886. doi: 10.1371/journal.pone.0099886
  • Okumura T, Kojima H, Miwa T, et al. The expression of microRNA 574-3p as a predictor of postoperative outcome in patients with esophageal squamous cell carcinoma. World J Surg Oncol. 2016;14(1):228. doi: 10.1186/s12957-016-0985-3
  • Lee EK, et al. Nc886, a non-coding RNA and suppressor of PKR, exerts an oncogenic function in thyroid cancer. Oncotarget. 2016;7(46):75000–75012. doi: 10.18632/oncotarget.11852
  • Ortega-García MB, et al. Uncovering tumour heterogeneity through PKR and nc886 analysis in metastatic colon cancer patients treated with 5-FU-based chemotherapy. Cancers (Basel). 2020;12(2):379. doi: 10.3390/cancers12020379
  • Han Z-B, Zhong L, Teng M-J, et al. Identification of recurrence-related microRnas in hepatocellular carcinoma following liver transplantation. Mol Oncol. 2012;6(4):445–457. doi: 10.1016/j.molonc.2012.04.001
  • Yu M-C, Lee C-W, Lin C-H, et al. Differential hypermethylation of the vtRNA2-1 promoter in hepatocellular carcinoma as a prognostic factor: tumor marker prognostic study. Int J Surg. 2020;79:282–289. doi: 10.1016/j.ijsu.2020.05.016
  • Wang Z, Lu Y, Fornage M, et al. Identification of novel susceptibility methylation loci for pancreatic cancer in a two-phase epigenome-wide association study. Epigenetics. 2022;17(11):1357–1372. doi: 10.1080/15592294.2022.2026591
  • Paliwal A, et al. Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation. PLoS Genet. 2013;9(8):e1003622. doi: 10.1371/journal.pgen.1003622
  • Van Baak TE, et al. Epigenetic supersimilarity of monozygotic twin pairs. Genome Bio. 2018;19(2). doi: 10.1186/s13059-017-1374-0
  • Schulze KV, Swaminathan S, Howell S, et al. Edematous severe acute malnutrition is characterized by hypomethylation of DNA. Nat Commun. 2019;10(1):5791. doi: 10.1038/s41467-019-13433-6
  • Kho M, et al. Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of arteriopathy (GENOA) study. BMC Med Genomics. 2020;13(1):131. doi: 10.1186/s12920-020-00791-0
  • Quinn EB, Hsiao CJ, Maisha FM, et al. Prenatal maternal stress is associated with site-specific and age acceleration changes in maternal and newborn DNA methylation. Epigenetics. 2023;18(1):2222473. doi: 10.1080/15592294.2023.2222473
  • Galanter JM, Gignoux CR, Oh SS, et al. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures. Elife. 2017;6:e20532. doi: 10.7554/eLife.20532
  • Xiu J, Li J, Liu Z, et al. Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice. Proc Natl Acad Sci U S A. 2022;119(30):e2201967119. doi: 10.1073/pnas.2201967119
  • Kao W-Y, Yang S-H, Liu W-J, et al. Genome-wide identification of blood DNA methylation patterns associated with early-onset hepatocellular carcinoma development in hepatitis B carriers. Mol Carcinog. 2017;56(2):425–435. doi: 10.1002/mc.22505
  • Horvath S, Ritz BR. Increased epigenetic age and granulocyte counts in the blood of Parkinson’s disease patients. Aging (Albany NY). 2015;7:1130–1142. doi:10.18632/aging.100859
  • Horvath S, et al. Huntington’s disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels. Aging (Albany NY). 2016;8:1485–1512. doi: 10.18632/aging.101005
  • Hannum G, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Molecular Cell. 2013;49(2):359–367. doi: 10.1016/j.molcel.2012.10.016
  • Horvath S, Erhart W, Brosch M, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci USA. 2014;111(43):15538–15543. doi: 10.1073/pnas.1412759111
  • Johnson ND, Wu X, Still CD, et al. Differential DNA methylation and changing cell-type proportions as fibrotic stage progresses in NAFLD. Clin Epigenetics. 2021;13(1):152. doi: 10.1186/s13148-021-01129-y
  • Roos L, Sandling JK, Bell CG, et al. Higher nevus Count exhibits a distinct DNA methylation signature in healthy human skin: implications for melanoma. J Invest Dermatol. 2017;137(4):910–920. doi: 10.1016/j.jid.2016.11.029
  • Kirby MK, Ramaker RC, Roberts BS, et al. Genome-wide DNA methylation measurements in prostate tissues uncovers novel prostate cancer diagnostic biomarkers and transcription factor binding patterns. BMC Cancer. 2017;17(1):273. doi: 10.1186/s12885-017-3252-2
  • Oliva M, Demanelis K, Lu Y, et al. DNA methylation QTL mapping across diverse human tissues provides molecular links between genetic variation and complex traits. Nat Genet. 2023;55(1):112–122. doi: 10.1038/s41588-022-01248-z
  • Johnson KC, Houseman EA, King JE, et al. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age. Breast Cancer Res. 2017;19(1):81. doi: 10.1186/s13058-017-0873-y
  • Song M-A, Brasky TM, Weng DY, et al. Landscape of genome-wide age-related DNA methylation in breast tissue. Oncotarget. 2017;8(70):114648–114662. doi: 10.18632/oncotarget.22754
  • Wei J-H, Haddad A, Wu K-J, et al. A CpG-methylation-based assay to predict survival in clear cell renal cell carcinoma. Nat Commun. 2015;6(1):8699. doi: 10.1038/ncomms9699