Salivary Exosomal miRNA-1307-5p Predicts Disease Aggressiveness and Poor Prognosis in Oral Squamous Cell Carcinoma Patients

被引:32
作者
Patel, Aditi [1 ]
Patel, Shanaya [1 ]
Patel, Parina [1 ]
Mandlik, Dushyant [2 ]
Patel, Kaustubh [2 ]
Tanavde, Vivek [1 ,3 ]
机构
[1] Ahmedabad Univ, Sch Arts & Sci, Biol & Life Sci, Ahmadabad 380009, Gujarat, India
[2] HCG Canc Ctr, Dept Head & Neck Oncol, Ahmadabad 380060, Gujarat, India
[3] ASTAR, Bioinformat Inst, Singapore 138671, Singapore
关键词
oral cancer; exosomes; saliva; microRNAs; prognosis; chemoresistance; CANCER;
D O I
10.3390/ijms231810639
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. Method: Small RNA and transcriptome sequencing profiles of tumour tissues (n = 12) and salivary exosomes (n = 8) from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using The Cancer Genome Atlas database and performing Real-time PCR on a large patient cohort (n = 19 tissue samples; n = 12 salivary exosomes). Potential target genes and the miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. Results: Salivary exosomes (size: 30-50 nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4 and RNF114. Conclusions: Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.
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页数:18
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共 39 条
  • [11] The Emerging Role of Exosomes in Diagnosis, Prognosis, and Therapy in Head and Neck Cancer
    Hofmann, Linda
    Ludwig, Sonja
    Vahl, Julius M.
    Brunner, Cornelia
    Hoffmann, Thomas K.
    Theodoraki, Marie-Nicole
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (11) : 1 - 22
  • [12] A novel miR-365-3p/EHF/keratin 16 axis promotes oral squamous cell carcinoma metastasis, cancer stemness and drug resistance via enhancing 5-integrin/c-met signaling pathway
    Huang, Wei-Chieh
    Jang, Te-Hsuan
    Tung, Shiao-Lin
    Yen, Tzu-Chen
    Chan, Shih-Hsuan
    Wang, Lu-Hai
    [J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (1)
  • [13] A PML-PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance
    Ito, Keisuke
    Carracedo, Arkaitz
    Weiss, Dror
    Arai, Fumio
    Ala, Ugo
    Avigan, David E.
    Schafer, Zachary T.
    Evans, Ronald M.
    Suda, Toshio
    Lee, Chih-Hao
    Pandolfi, Pier Paolo
    [J]. NATURE MEDICINE, 2012, 18 (09) : 1350 - +
  • [14] CD63, MHC class 1, and CD47 identify subsets of extracellular vesicles containing distinct populations of noncoding RNAs
    Kaur, Sukhbir
    Elkahloun, Abdel G.
    Arakelyan, Anush
    Young, Lynn
    Myers, Timothy G.
    Otaizo-Carrasquero, Francisco
    Wu, Weiwei
    Margolis, Leonid
    Roberts, David D.
    [J]. SCIENTIFIC REPORTS, 2018, 8
  • [15] GET4 is a novel driver gene in colorectal cancer that regulates the localization of BAG6, a nucleocytoplasmic shuttling protein
    Koike, Kensuke
    Masuda, Takaaki
    Sato, Kuniaki
    Fujii, Atsushi
    Wakiyama, Hiroaki
    Tobo, Taro
    Takahashi, Junichi
    Motomura, Yushi
    Nakano, Takafumi
    Saito, Hideyuki
    Matsumoto, Yoshihiro
    Otsu, Hajime
    Takeishi, Kazuki
    Yonemura, Yusuke
    Mimori, Koshi
    Nakagawa, Takashi
    [J]. CANCER SCIENCE, 2022, 113 (01) : 156 - 169
  • [16] Clinical significance of GET4 expression in colorectal cancer
    Koike, Kensuke
    Masuda, Takaaki
    Sato, Kuniaki
    Motomura, Yuushi
    Takahashi, Jyunnichi
    Shimizu, Dai
    Kuramitsu, Shotaro
    Fujii, Atsushi
    Kitagawa, Akihiro
    Noda, Miwa
    Tsuruda, Yusuke
    Ootu, Hajime
    Kuroda, Yousuke
    Eguchi, Hidetoshi
    Nakagawa, Takashi
    Mimori, Koushi
    [J]. CANCER RESEARCH, 2019, 79 (13)
  • [17] Comprehensive microRNA-sequencing of exosomes derived from head and neck carcinoma cells in vitro reveals common secretion profiles and potential utility as salivary biomarkers
    Langevin, Scott
    Kuhnell, Damaris
    Parry, Tess
    Biesiada, Jacek
    Huang, Shouxiong
    Wise-Draper, Trisha
    Casper, Keith
    Zhang, Xiang
    Medvedovic, Mario
    Kasper, Susan
    [J]. ONCOTARGET, 2017, 8 (47) : 82459 - 82474
  • [18] Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers
    Lee, Eunjee
    Ito, Koichi
    Zhao, Yong
    Schadt, Eric E.
    Irie, Hanna Y.
    Zhu, Jun
    [J]. BIOINFORMATICS, 2016, 32 (01) : 96 - 105
  • [19] Martin M., 2011, EMBnet.journal, V17, P10, DOI [10.14806/ej.17.1.200, https://doi.org/10.14806/ej.17.1.200]
  • [20] NARASIMHAN NS, 2018, BIOMED PHARMACOL J, V11, P1961, DOI DOI 10.13005/bpj/1569