miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

Yang,Qin; Zhao,Qiuling; Yin,Yanliang

doi:10.3892/etm.2019.7855

miR‑133b is a potential diagnostic biomarker for Alzheimer's disease and has a neuroprotective role

Authors:
- Qin Yang
- Qiuling Zhao
- Yanliang Yin
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Affiliations: Department of Neurology, Dongying People's Hospital, Dongcheng, Shandong 257091, P.R. China, Digestive Endoscopy Center, Dongying People's Hospital, Dongcheng, Shandong 257091, P.R. China, Department of Health Care, Dongying People's Hospital, Dongcheng, Shandong 257091, P.R. China
Published online on: August 5, 2019 https://doi.org/10.3892/etm.2019.7855
Pages: 2711-2718

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Abstract

MicroRNAs (miRNAs/miRs) are involved in post‑transcriptional gene regulation and aberrant expression of miRNAs has been widely detected in various human diseases. The aim of the present study was to examine the serum levels of miR‑133b in patients with Alzheimer's disease (AD), and to explore its diagnostic value and neuroprotective role in AD. Reverse transcription‑quantitative PCR was applied to analyze the serum levels of miR‑133b in 105 AD patients and 98 healthy controls. A cell model of AD was established by treating SH‑SY5Y cells with amyloid β (Aβ)25‑35, and the resulting effect on miR‑133b expression was determined. Cell viability and apoptosis were also measured. A dual‑luciferase assay was used to validate a target gene of miR‑133b. Receiver operating characteristic (ROC) curve analysis was also applied to assess the specificity and sensitivity of miR‑133b to diagnose AD. The results indicated that the serum levels of miR‑133b were significantly downregulated in AD patients and SH‑SY5Y cells treated with Aβ25‑35 (all P<0.001). A positive correlation between the serum levels of miR‑133b and the Mini‑Mental State Examination score of AD patients was determined (r=0.8814, P<0.001). The area under the ROC curve for miR‑133b regarding the diagnosis of AD was 0.907, with a sensitivity of 90.8% and specificity of 74.3% at the cutoff value of 1.70. Overexpression of miR‑133b significantly attenuated the Aβ25‑35‑induced inhibition of cell viability (P<0.01) and induction of cell apoptosis (P<0.01). The luciferase reporter assay demonstrated that epidermal growth factor receptor (EGFR) is a target gene of miR‑133b. In conclusion, miR‑133b may serve as a novel diagnostic biomarker for AD and it may have a neuroprotective role in AD and targets EGFR.

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1	Balin BJ and Hudson AP: Etiology and pathogenesis of late-onset Alzheimer's disease. Curr Allergy Asthma Rep. 14:4172014. View Article : Google Scholar : PubMed/NCBI
2	Gu QF, Yu JZ, Wu H, Li YH, Liu CY, Feng L, Zhang GX, Xiao BG and Ma CG: Therapeutic effect of Rho kinase inhibitor FSD-C10 in a mouse model of Alzheimer's disease. Exp Ther Med. 16:3929–3938. 2018.PubMed/NCBI
3	Alzheimer's Association National Plan Milestone Workgroup, Fargo KN, Aisen P, Albert M, Au R, Corrada MM, DeKosky S, Drachman D, Fillit H, Gitlin L, et al: 2014 report on the milestones for the US national plan to address Alzheimer's disease. Alzheimers Dement 10 (5 Suppl). S430–S452. 2014.
4	Mayeux R and Stern Y: Epidemiology of Alzheimer disease. Cold Spring Harb Perspect Med. 2(pii): a0062392012.PubMed/NCBI
5	Tan MS, Yu JT and Tan L: Bridging integrator 1 (BIN1): Form, function, and Alzheimer's disease. Trends Mol Med. 19:594–603. 2013. View Article : Google Scholar : PubMed/NCBI
6	Bekris LM, Yu CE, Bird TD and Tsuang DW: Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol. 23:213–227. 2010. View Article : Google Scholar : PubMed/NCBI
7	Paul S: Integration of miRNA and mRNA expression data for understanding etiology of gynecologic cancers. Methods Mol Biol 1912. 323–338. 2019. View Article : Google Scholar
8	Huang X, Liang M, Dittmar R and Wang L: Extracellular microRNAs in urologic malignancies: chances and challenges. Int J Mol Sci. 14:14785–14799. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kumar S, Vijayan M and Reddy PH: MicroRNA-455-3p as a potential peripheral biomarker for Alzheimer's disease. Hum Mol Genet. 26:3808–3822. 2017. View Article : Google Scholar : PubMed/NCBI
10	Hong H, Li Y and Su B: Identification of circulating miR-125b as a potential biomarker of Alzheimer's disease in APP/PS1 transgenic mouse. J Alzheimers Dis. 59:1449–1458. 2017. View Article : Google Scholar : PubMed/NCBI
11	Tao J, Wu D, Xu B, Qian W, Li P, Lu Q, Yin C and Zhang W: microRNA-133 inhibits cell proliferation, migration and invasion in prostate cancer cells by targeting the epidermal growth factor receptor. Oncol Rep. 27:1967–1975. 2012.PubMed/NCBI
12	Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G and Abeliovich A: A MicroRNA feedback circuit in midbrain dopamine neurons. Science. 317:1220–1224. 2007. View Article : Google Scholar : PubMed/NCBI
13	Goedert M: NEURODEGENERATION. Alzheimer's and Parkinson's diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein. Science. 349:12555552015. View Article : Google Scholar : PubMed/NCBI
14	Zhao N, Jin L, Fei G, Zheng Z and Zhong C: Serum microRNA-133b is associated with low ceruloplasmin levels in Parkinson's disease. Parkinsonism Relat Disord. 20:1177–1180. 2014. View Article : Google Scholar : PubMed/NCBI
15	Zhang X, Yang R, Hu BL, Lu P, Zhou LL, He ZY, Wu HM and Zhu JH: Reduced circulating levels of miR-433 and miR-133b are potential biomarkers for Parkinson's disease. Front Cell Neurosci. 11:1702017. View Article : Google Scholar : PubMed/NCBI
16	Niu M, Xu R, Wang J, Hou B and Xie A: MiR-133b ameliorates axon degeneration induced by MPP(+) via targeting RhoA. Neuroscience. 325:39–49. 2016. View Article : Google Scholar : PubMed/NCBI
17	Igawa S, Ryuge S, Ichinoe M, Nakashima H, Otani S, Nakahara Y, Fukui T, Sasaki J, Kubota M, Katagiri M, et al: Impact of EGFR-tyrosine kinase inhibitors on postoperative recurrent non-small-cell lung cancer harboring EGFR mutations. Oncol Res Treat. 40:7–13. 2017. View Article : Google Scholar : PubMed/NCBI
18	Tanaka T, Kaida T, Yokoi K, Ishii S, Nishizawa N, Kawamata H, Katoh H, Sato T, Nakamura T, Watanabe M and Yamashita K: Critical relevance of genomic gains of PRL-3/EGFR/c-myc pathway genes in liver metastasis of colorectal cancer. Oncol Lett. 17:1257–1266. 2019.PubMed/NCBI
19	Guo N, Zhao Y, Zhang W, Li S and Yu J: MicroRNA-133a downregulated EGFR expression in human non-small cell lung cancer cells via AKT/ERK signaling. Oncol Lett. 16:6045–6050. 2018.PubMed/NCBI
20	Bruban J, Voloudakis G, Huang Q, Kajiwara Y, Al Rahim M, Yoon Y, Shioi J, Gama Sosa MA, Shao Z, Georgakopoulos A and Robakis NK: Presenilin 1 is necessary for neuronal, but not glial, EGFR expression and neuroprotection via γ-secretase-independent transcriptional mechanisms. FASEB J. 29:3702–3712. 2015. View Article : Google Scholar : PubMed/NCBI
21	Zeng W, Zhu JF, Liu JY, Li YL, Dong X, Huang H and Shan L: miR-133b inhibits cell proliferation, migration and invasion of esophageal squamous cell carcinoma by targeting EGFR. Biomed Pharmacother. 111:476–484. 2018. View Article : Google Scholar : PubMed/NCBI
22	Lugli G, Cohen AM, Bennett DA, Shah RC, Fields CJ, Hernandez AG and Smalheiser NR: Plasma exosomal miRNAs in persons with and without Alzheimer disease: Altered expression and prospects for biomarkers. PLoS One. 10:e01392332015. View Article : Google Scholar : PubMed/NCBI
23	Whitworth JA; World Health Organization and International Society of Hypertension Writing Group, : 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 21:1983–1992. 2003. View Article : Google Scholar : PubMed/NCBI
24	Puavilai G, Chanprasertyotin S and Sriphrapradaeng A: Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the expert committee on the diagnosis and classification of diabetes mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Diabetes Res Clin Pract. 44:21–26. 1999. View Article : Google Scholar : PubMed/NCBI
25	Zhang B, Qiu Q, Yin L, Yao Y, Wang C and Wu X: Measurement of retinal function with flash-electroretinography in Chinese patients with hyperlipidemia. Graefes Arch Clin Exp Ophthalmol. 252:1385–1392. 2014. View Article : Google Scholar : PubMed/NCBI
26	Wang X, Zhao X, Li L, Yao H, Jiang Y and Zhang J: Effects of Combination of ezetimibe and rosuvastatin on coronary artery plaque in patients with coronary heart disease. Heart Lung Circ. 25:459–465. 2016. View Article : Google Scholar : PubMed/NCBI
27	Li H, Jia J and Yang Z: Mini-mental state examination in elderly chinese: A population-based normative study. J Alzheimers Dis. 53:487–496. 2016. View Article : Google Scholar : PubMed/NCBI
28	Hu L, Zhang R, Yuan Q, Gao Y, Yang MQ, Zhang C, Huang J, Sun Y, Yang W, Yang JY, et al: The emerging role of microRNA-4487/6845-3p in Alzheimer's disease pathologies is induced by Aβ25–35 triggered in SH-SY5Y cell. BMC Syst Biol. 12 (Suppl 7):S1192018. View Article : Google Scholar
29	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
30	Amodio N, Stamato MA, Gullà AM, Morelli E, Romeo E, Raimondi L, Pitari MR, Ferrandino I, Misso G, Caraglia M, et al: Therapeutic targeting of miR-29b/HDAC4 epigenetic loop in multiple myeloma. Mol Cancer Ther. 15:1364–1375. 2016. View Article : Google Scholar : PubMed/NCBI
31	Tian Y, Yan M, Zheng J, Li R, Lin J, Xu A, Liang Y, Zheng R and Yuan Y: miR-483-5p decreases the radiosensitivity of nasopharyngeal carcinoma cells by targeting DAPK1. Lab Invest. 99:602–611. 2019. View Article : Google Scholar : PubMed/NCBI
32	Maniati MS, Maniati M, Yousefi T, Ahmadi-Ahangar A and Tehrani SS: New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases. J Cell Biochem. 120:8908–8918. 2019. View Article : Google Scholar : PubMed/NCBI
33	Díaz NF, Cruz-Reséndiz MS, Flores-Herrera H, García-López G and Molina-Hernández A: MicroRNAs in central nervous system development. Rev Neurosci. 25:675–686. 2014.PubMed/NCBI
34	Maldonado-Lasuncion I, Atienza M, Sanchez-Espinosa MP and Cantero JL: Aging-related changes in cognition and cortical integrity are associated with serum expression of candidate MicroRNAs for Alzheimer disease. Cereb Cortex. Dec 22–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
35	Shi Z, Kadeer A, Wang M, Wen B, Li M, Huang J, Gao Y, Liu E, Liu D, Jia D and Liang C: The deregulation of miR-133b is associated with poor prognosis in bladder cancer. Pathol Res Pract. 215:354–357. 2019. View Article : Google Scholar : PubMed/NCBI
36	Wang QY, Zhou CX, Zhan MN, Tang J, Wang CL, Ma CN, He M, Chen GQ, He JR and Zhao Q: MiR-133b targets Sox9 to control pathogenesis and metastasis of breast cancer. Cell Death Dis. 9:7522018. View Article : Google Scholar : PubMed/NCBI
37	Zhang Q, Fan X, Xu B, Pang Q and Teng L: miR-133b acts as a tumor suppressor and negatively regulates EMP2 in glioma. Neoplasma. 65:494–504. 2018. View Article : Google Scholar : PubMed/NCBI
38	Thaker AA, Weinberg BD, Dillon WP, Hess CP, Cabral HJ, Fleischman DA, Leurgans SE, Bennett DA, Hyman BT, Albert MS, et al: Entorhinal cortex: Antemortem cortical thickness and postmortem neurofibrillary tangles and amyloid pathology. AJNR Am J Neuroradiol. 38:961–965. 2017. View Article : Google Scholar : PubMed/NCBI
39	Arevalo-Rodriguez I, Smailagic N, Roqué I Figuls M, Ciapponi A, Sanchez-Perez E, Giannakou A, Pedraza OL, Bonfill Cosp X and Cullum S: Mini-mental state examination (MMSE) for the detection of Alzheimer's disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev. CD0107832015.PubMed/NCBI
40	Li H, Xiang Z, Liu Y, Xu B and Tang J: MicroRNA-133b inhibits proliferation, cellular migration, and invasion via targeting LASP1 in hepatocarcinoma cells. Oncol Res. 25:1269–1282. 2017. View Article : Google Scholar : PubMed/NCBI
41	Zhen Y, Liu J, Huang Y, Wang Y, Li W and Wu J: miR-133b inhibits cell growth, migration, and invasion by targeting MMP9 in non-small cell lung cancer. Oncol Res. 25:1109–1116. 2017. View Article : Google Scholar : PubMed/NCBI
42	Appert-Collin A, Hubert P, Crémel G and Bennasroune A: Role of ErbB receptors in cancer cell migration and invasion. Front Pharmacol. 6:2832015. View Article : Google Scholar : PubMed/NCBI
43	Kim SB, Ly P, Kaisani A, Zhang L, Wright WE and Shay JW: Mitigation of radiation-induced damage by targeting EGFR in noncancerous human epithelial cells. Radiat Res. 180:259–267. 2013. View Article : Google Scholar : PubMed/NCBI
44	Yarden Y and Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2:127–137. 2001. View Article : Google Scholar : PubMed/NCBI
45	Guillot F, Kemppainen S, Lavasseur G, Miettinen PO, Laroche S, Tanila H and Davis S: Brain-specific basal and novelty-induced alternations in PI3K-Akt and MAPK/ERK signaling in a middle-aged AβPP/PS1 mouse model of Alzheimer's disease. J Alzheimers Dis. 51:1157–1173. 2016. View Article : Google Scholar : PubMed/NCBI
46	Feng MG, Liu CF, Chen L, Feng WB, Liu M, Hai H and Lu JM: MiR-21 attenuates apoptosis-triggered by amyloid-β via modulating PDCD4/PI3K/AKT/GSK-3β pathway in SH-SY5Y cells. Biomed Pharmacother. 101:1003–1007. 2018. View Article : Google Scholar : PubMed/NCBI
47	Zang G, Fang L, Chen L and Wang C: Ameliorative effect of nicergoline on cognitive function through the PI3K/AKT signaling pathway in mouse models of Alzheimer's disease. Mol Med Rep. 17:7293–7300. 2018.PubMed/NCBI