Abstract
This study aims to evaluate the effect of peripheral blood miR-125b expression on severity and prognosis in children with viral encephalitis (VE). Children with VE (severe and mild groups) were grouped into VE group, and 40 healthy children as control group. Plasma RNA was extracted, and real-time quantitative PCR was conducted to detect miR-125b relative expression. Associations of miR-125b expression with clinical characteristics and prognosis of VE children were analyzed. Area under ROC curve (AUC) was calculated to evaluate the accuracy of the prognostic value of miR-125b. Univariate analysis and logistic regression analysis were performed to analyze risk factors of the prognoses of VE children. The plasma miR-125b expression was higher in the VE group than in the control group and higher in the severe group than the mild group. MiR-125b expression was associated with status convulsion, hemiplegia, multiple organ injuries, and stress hyperglycemia in VE children. Patients with poor prognosis exhibited higher miR-125b expression than those with good prognosis, and the rate of high miR-125b expression of the patients with poor prognosis (64.10%, 25/39) was higher than that in those with good prognosis (28.92%, 24/83). The AUC of miR-125b expression to predict prognosis of VE children was 0.833. When the cutoff value was 1.715, the diagnostic sensitivity (87.2%), specificity (71.1%), and accuracy (76.2%) were the highest. Status convulsion, stress hyperglycemia, and miR-125b were considered as risk factors for poor prognosis in VE children. Peripheral blood miR-125b expression may be correlated with the severity and prognosis of VE in children.
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Domingues RB (2012) Viral encephalitis: current treatments and future perspectives. Cent Nerv Syst Agents Med Chem 12(4):277–285
Silva MT (2013) Viral encephalitis. Arq Neuropsiquiatr 71(9B):703–709. doi:10.1590/0004-282X20130155
Domingues RB (2009) Treatment of viral encephalitis. Cent Nerv Syst Agents Med Chem 9(1):56–62
Thompson C, Kneen R, Riordan A, Kelly D, Pollard AJ (2012) Encephalitis in children. Arch Dis Child 97(2):150–161. doi:10.1136/archdischild-2011-300100
Piquet AL, Cho TA (2016) The clinical approach to encephalitis. Current neurology and neuroscience reports 16(5):45. doi:10.1007/s11910-016-0650-9
Zhao L, Zhou M, Wang B, Guo J, Chen N, He L (2015) Clinical characteristics and outcome of clinically diagnosed viral encephalitis in southwest China. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 36(12):2191–2197. doi:10.1007/s10072-015-2333-8
Chan BK, Wilson T, Fischer KF, Kriesel JD (2014) Deep sequencing to identify the causes of viral encephalitis. PLoS One 9(4):e93993. doi:10.1371/journal.pone.0093993
Dhanze H, Bhilegaonkar KN, Ravi Kumar GV, Thomas P, Chethan Kumar HB, Suman Kumar M, Rawat S, Kerketta P, Rawool DB, Kumar A (2015) Comparative evaluation of nucleic acid-based assays for detection of Japanese encephalitis virus in swine blood samples. Arch Virol 160(5):1259–1266. doi:10.1007/s00705-015-2385-3
Banzhaf-Strathmann J, Edbauer D (2014) Good guy or bad guy: the opposing roles of microRNA 125b in cancer. Cell communication and signaling : CCS 12:30. doi:10.1186/1478-811X-12-30
Huang K, Dong S, Li W, Xie Z (2013) The expression and regulation of microRNA-125b in cancers. Acta Biochim Biophys Sin 45(10):803–805. doi:10.1093/abbs/gmt073
Cui EH, Li HJ, Hua F, Wang B, Mao W, Feng XR, Li JY, Wang X (2013) Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin 34(2):309–313. doi:10.1038/aps.2012.125
Wei X, Chen D, Lv T, Li G, Qu S (2016) Serum MicroRNA-125b as a potential biomarker for glioma diagnosis. Mol Neurobiol 53(1):163–170. doi:10.1007/s12035-014-8993-1
Gottwein E, Cullen BR (2008) Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 3(6):375–387. doi:10.1016/j.chom.2008.05.002
Wang FZ, Weber F, Croce C, Liu CG, Liao X, Pellett PE (2008) Human cytomegalovirus infection alters the expression of cellular microRNA species that affect its replication. J Virol 82(18):9065–9074. doi:10.1128/JVI.00961-08
Skalsky RL, Cullen BR (2010) Viruses, microRNAs, and host interactions. Annu Rev Microbiol 64:123–141. doi:10.1146/annurev.micro.112408.134243
Jangra RK, Yi M, Lemon SM (2010) Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 84(13):6615–6625. doi:10.1128/JVI.00417-10
Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saib A, Voinnet O (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308(5721):557–560. doi:10.1126/science.1108784
Wang P, Hou J, Lin L, Wang C, Liu X, Li D, Ma F, Wang Z, Cao X (2010) Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol 185(10):6226–6233. doi:10.4049/jimmunol.1000491
Mantri CK, Pandhare Dash J, Mantri JV, Dash CC (2012) Cocaine enhances HIV-1 replication in CD4+ T cells by down-regulating MiR-125b. PLoS One 7(12):e51387. doi:10.1371/journal.pone.0051387
Ninomiya M, Kondo Y, Kimura O, Funayama R, Nagashima T, Kogure T, Morosawa T, Tanaka Y, Nakayama K, Shimosegawa T (2016) The expression of miR-125b-5p is increased in the serum of patients with chronic hepatitis B infection and inhibits the detection of hepatitis B virus surface antigen. J Viral Hepat 23(5):330–339. doi:10.1111/jvh.12522
Sun YM, Lin KY, Chen YQ (2013) Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol 6:6. doi:10.1186/1756-8722-6-6
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262
Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, Stahl JP, Mailles A, Drebot M, Rupprecht CE, Yoder J, Cope JR, Wilson MR, Whitley RJ, Sullivan J, Granerod J, Jones C, Eastwood K, Ward KN, Durrheim DN, Solbrig MV, Guo-Dong L, Glaser CA, International Encephalitis C (2013) Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 57(8):1114–1128. doi:10.1093/cid/cit458
Sharma S, Mishra D, Aneja S, Kumar R, Jain A, Vashishtha VM, Expert Group on Encephalitis IAoP (2012) Consensus guidelines on evaluation and management of suspected acute viral encephalitis in children in India. Indian Pediatr 49(11):897–910
Cooper J, Kierans C, Defres S, Easton A, Kneen R, Solomon T (2016) Diagnostic pathways as social and participatory practices: the case of herpes simplex encephalitis. PLoS One 11(3):e0151145. doi:10.1371/journal.pone.0151145
Yang FH, Wang H, Zhang JM, Zhang H, Pan LL (2008) Changes and roles of VEGF and VCAM-1 in cerebrospinal fluid of children with viral encephalitis. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 10(3):285–289
Chang CY, Li JR, Chen WY, Ou YC, Lai CY, Hu YH, Wu CC, Chang CJ, Chen CJ (2015) Disruption of in vitro endothelial barrier integrity by Japanese encephalitis virus-infected astrocytes. Glia. doi:10.1002/glia.22857
Chitumalla RK, Gupta KS, Malapaka C, Fallahpour R, Islam A, Han L, Kotamarthi B, Singh SP (2014) Thiocyanate-free cyclometalated ruthenium(II) sensitizers for DSSC: a combined experimental and theoretical investigation. Physical chemistry chemical physics : PCCP 16(6):2630–2640. doi:10.1039/c3cp53613k
Smits M, Wurdinger T, van het Hof B, Drexhage JA, Geerts D, Wesseling P, Noske DP, Vandertop WP, de Vries HE, Reijerkerk A (2012) Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26(6):2639–2647. doi:10.1096/fj.11-202820
Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179(8):5082–5089
Hayasaka D, Shirai K, Aoki K, Nagata N, Simantini DS, Kitaura K, Takamatsu Y, Gould E, Suzuki R, Morita K (2013) TNF-alpha acts as an immunoregulator in the mouse brain by reducing the incidence of severe disease following Japanese encephalitis virus infection. PLoS One 8(8):e71643. doi:10.1371/journal.pone.0071643
Wu JG, Wang JJ, Jiang X, Lan JP, He XJ, Wang HJ, Ma YY, Xia YJ, Ru GQ, Ma J, Zhao ZS, Zhou R (2015) MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 18(4):729–739. doi:10.1007/s10120-014-0421-8
Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C, Croce CM (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 297(17):1901–1908. doi:10.1001/jama.297.17.1901
Shi XB, Xue L, Ma AH, Tepper CG, Kung HJ, White RW (2011) miR-125b promotes growth of prostate cancer xenograft tumor through targeting pro-apoptotic genes. Prostate 71(5):538–549. doi:10.1002/pros.21270
Nelson PT, Baldwin DA, Kloosterman WP, Kauppinen S, Plasterk RH, Mourelatos Z (2006) RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA 12(2):187–191. doi:10.1261/rna.2258506
Nishida N, Yokobori T, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Kuwano H, Mori M (2011) MicroRNA miR-125b is a prognostic marker in human colorectal cancer. Int J Oncol 38(5):1437–1443. doi:10.3892/ijo.2011.969
Karbasy SH, Taheriazam A, Mirghasemi A, Sedaghati F, Shakeri M, Yahaghi E, Bahador R (2015) Retracted article: upregulation of miR-300 and downregulation of miR-125b act as potential predictor biomarkers in progression, metastasis, and poor prognosis of osteosarcoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. doi:10.1007/s13277-015-4000-3
Zuberi M, Khan I, Mir R, Gandhi G, Ray PC, Saxena A (2016) Utility of serum miR-125b as a diagnostic and prognostic indicator and its alliance with a panel of tumor suppressor genes in epithelial ovarian cancer. PLoS One 11(4):e0153902. doi:10.1371/journal.pone.0153902
Greco F, Cocuzza MD, Smilari P, Sorge G, Pavone L (2014) Nonconvulsive status epilepticus complicating epstein-barr virus encephalitis in a child. Case reports in pediatrics 2014:547396. doi:10.1155/2014/547396
Vachalova I, Kyavar L, Heckmann JG (2013) Pitfalls associated with the diagnosis of herpes simplex encephalitis. Journal of neurosciences in rural practice 4(2):176–179. doi:10.4103/0976-3147.112756
Jiang F, Liu T, He Y, Yan Q, Chen X, Wang H, Wan X (2011) MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. BMC Cancer 11:425. doi:10.1186/1471-2407-11-425
Fassan M, Pizzi M, Realdon S, Balistreri M, Guzzardo V, Zagonel V, Castoro C, Mastracci L, Farinati F, Nitti D, Zaninotto G, Rugge M (2013) The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis. Hum Pathol 44(9):1804–1810. doi:10.1016/j.humpath.2013.01.023
Wu N, Xiao L, Zhao X, Zhao J, Wang J, Wang F, Cao S, Lin X (2012) miR-125b regulates the proliferation of glioblastoma stem cells by targeting E2F2. FEBS Lett 586(21):3831–3839. doi:10.1016/j.febslet.2012.08.023
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Gao, QL., Ma, YX., Yuan, DW. et al. MicroRNA-125b in peripheral blood: a potential biomarker for severity and prognosis of children with viral encephalitis. Neurol Sci 38, 1437–1444 (2017). https://doi.org/10.1007/s10072-017-2982-x
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DOI: https://doi.org/10.1007/s10072-017-2982-x