Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening

被引:141
作者
He, Lihong [1 ,2 ]
Ping, Fan [1 ,2 ]
Fan, Zhaona [1 ,2 ]
Zhang, Chi [1 ,2 ]
Deng, Miao [1 ,2 ]
Cheng, Bin [1 ,2 ]
Xia, Juan [1 ,2 ]
机构
[1] Sun Yat Sen Univ, Hosp Stomatol, Dept Oral Med, Guangzhou, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Guanghua Sch Stomatol, Guangdong Prov Key Lab Stomatol, Guangzhou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Oral squamous cell carcinoma; Salivary exosomes; miR-24-3p; Diagnostic biomarker; PER1; CIRCADIAN CLOCK; SERUM MIR-21; GENE PER1; CANCER; PROLIFERATION; MICRORNAS; PROMOTES; GROWTH; OVEREXPRESSION; RESISTANCE;
D O I
10.1016/j.biopha.2019.109553
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objectives: miRNAs in salivary exosomes are used as novel non-invasive biomarkers for detection strategies of human disease. Here, we aimed to investigate the diagnostic potential of salivary exosomal miRNAs as biomarkers for screening oral squamous cell carcinoma (OSCC) and to explore the underlying mechanisms of OSCC pathogenesis. Materials and methods: Differentially expressed miRNAs were obtained from salivary exosomes of four healthy controls and four OSCC patients using miRNA microarray analysis. The expression of miR-24-3p in the salivary exosomes was then verified by qRT-PCR. The diagnostic power was assessed by receiver operating characteristic (ROC) analysis. Cell proliferation was measured using CCK-8 cell viability assay and colony formation assay. The target gene of miR-24-3p was confirmed by dual luciferase reporter assay. Results: A total of 109 miRNAs were found to be more than 2-fold altered in the salivary of patients and healthy individuals by miRNA microarray. qRT-PCR analysis further confirmed a significant increase of miR-24-3p in the salivary exosomes from 45 preoperative OSCC patients compared to 10 normal controls. ROC analysis showed that miR-24-3p has excellent diagnostic accuracy for OSCC (area under the ROC curve [AUC] = 0.738; P = 0.02). Similarly, we found that miR-24-3p expressed a higher level in OSCC neoplastic tissues, suggesting that circulating miR-24-3p may originate from tumor cells. Furthermore, exogenous exosomal miR-24-3p increased proliferation of recipient malignant cells. Additionally, overexpression of miR-24-3p promoted the proliferation of OSCC cells and regulated the expression of cell cycle-related genes. Dual luciferase reporter assay indicated that miR-24-3p can interact with PER1 directly. Conclusions: Salivary exosomal miR-24-3p is a potential novel diagnostic biomarker for OSCC, and miR-24-3p can maintain the proliferation of OSCC cells through targeting PER1.
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页数:10
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共 59 条
[1]   Differences in microRNA expression between melanoma and healthy adjacent skin [J].
Aksenenko, Mariya ;
Palkina, Nadezhda ;
Komina, Anna ;
Tashireva, Liubov ;
Ruksha, Tatiana .
BMC DERMATOLOGY, 2019, 19
[2]   An estimate of the total number of true human miRNAs [J].
Alles, Julia ;
Fehlmann, Tobias ;
Fischer, Ulrike ;
Backes, Christina ;
Galata, Valentina ;
Minet, Marie ;
Hart, Martin ;
Abu-Halima, Masood ;
Graesser, Friedrich A. ;
Lenhof, Hans-Peter ;
Keller, Andreas ;
Meese, Eckart .
NUCLEIC ACIDS RESEARCH, 2019, 47 (07) :3353-3364
[3]   Macromolecular Assemblies of the Mammalian Circadian Clock [J].
Aryal, Rajindra P. ;
Kwak, Pieter Bas ;
Tamayo, Alfred G. ;
Gebert, Michael ;
Chiu, Po-Lin ;
Walz, Thomas ;
Weitz, Charles J. .
MOLECULAR CELL, 2017, 67 (05) :770-+
[4]   The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva [J].
Bahn, Jae Hoon ;
Zhang, Qing ;
Li, Feng ;
Chan, Tak-Ming ;
Lin, Xianzhi ;
Kim, Yong ;
Wong, David T. W. ;
Xiao, Xinshu .
CLINICAL CHEMISTRY, 2015, 61 (01) :221-230
[5]   Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis [J].
Becker, Annette ;
Thakur, Basant Kumar ;
Weiss, Joshua Mitchell ;
Kim, Han Sang ;
Peinado, Hector ;
Lyden, David .
CANCER CELL, 2016, 30 (06) :836-848
[6]   NON-CODING RNAs IN DEVELOPMENT AND DISEASE: BACKGROUND, MECHANISMS, AND THERAPEUTIC APPROACHES [J].
Beermann, Julia ;
Piccoli, Maria-Teresa ;
Viereck, Janika ;
Thum, Thomas .
PHYSIOLOGICAL REVIEWS, 2016, 96 (04) :1297-1325
[7]   microRNA-1246 Is an Exosomal Biomarker for Aggressive Prostate Cancer [J].
Bhagirath, Divya ;
Thao Ly Yang ;
Bucay, Nathan ;
Sekhon, Kirandeep ;
Majid, Shahana ;
Shahryari, Varahram ;
Dahiya, Rajvir ;
Tanaka, Yuichiro ;
Saini, Sharanjot .
CANCER RESEARCH, 2018, 78 (07) :1833-1844
[8]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21609, 10.3322/caac.21492]
[9]   Diagnostic profiling of salivary exosomal microRNAs in oral lichen planus patients [J].
Byun, J-S ;
Hong, S-H ;
Choi, J-K ;
Jung, J-K ;
Lee, H-J .
ORAL DISEASES, 2015, 21 (08) :987-993
[10]   Metabolism-related microRNAs in maternal breast milk are influenced by premature delivery [J].
Carney, Molly C. ;
Tarasiuk, Andrij ;
DiAngelo, Susan L. ;
Silveyra, Patricia ;
Podany, Abigail ;
Birch, Leann L. ;
Paul, Ian M. ;
Kelleher, Shannon ;
Hicks, Steven D. .
PEDIATRIC RESEARCH, 2017, 82 (02) :226-236