Abstract: Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.

外泌体与膀胱癌：新的生物标志物和靶点

[1]AbbastabarM, SarfiM, GolestaniA, et al., 2020. Tumor-derived urinary exosomal long non-coding RNAs as diagnostic biomarkers for bladder cancer. EXCLI J, 19:301-310.

[2]BeckhamCJ, OlsenJ, YinPN, et al., 2014. Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression. J Urol, 192(2):583-592.

[3]BerrondoC, FlaxJ, KucherovV, et al., 2016. Expression of the long non-coding RNA hotair correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLoS ONE, 11(1):e0147236.

[4]CaiHZ, YangXJ, GaoY, et al., 2019. Exosomal microRNA-9-3p secreted from BMSCs downregulates ESM1 to suppress the development of bladder cancer. Mol Ther Nucleic Acids, 18:787-800.

[5]CaiXX, QuLL, YangJ, et al., 2020. Exosome-transmitted microRNA-133b inhibited bladder cancer proliferation by upregulating dual-specificity protein phosphatase 1. Cancer Med, 9(16):6009-6019.

[6]ChenCH, LuoYM, HeW, et al., 2020. Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer. J Clin Invest, 130(1):404-421.

[7]ChenX, ChenRX, WeiWS, et al., 2018. PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res, 24(24):6319-6330.

[8]ChristensenE, Birkenkamp-DemtröderK, SethiH, et al., 2019. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol, 37(18):1547-1557.

[9]de PalmaG, di LorenzoVF, KrolS, et al., 2019. Urinary exosomal shuttle RNA: promising cancer diagnosis biomarkers of lower urinary tract. Int J Biol Markers, 34(2):101-107.

[10]el AndaloussiS, MägerI, BreakefieldXO, et al., 2013. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov, 12(5):347-357.

[11]ElsharkawiF, ElsabahM, ShabayekM, et al., 2019. Urine and serum exosomes as novel biomarkers in detection of bladder cancer. Asian Pac J Cancer Prev, 20(7):2219-2224.

[12]FranzenCA, BlackwellRH, TodorovicV, et al., 2015. Urothelial cells undergo epithelial-to-mesenchymal transition after exposure to muscle invasive bladder cancer exosomes. Oncogenesis, 4(8):e163.

[13]FranzenCA, BlackwellRH, ForemanKE, et al., 2016. Urinary exosomes: the potential for biomarker utility, intercellular signaling and therapeutics in urological malignancy. J Urol, 195(5):1331-1339.

[14]HuangCS, HoJY, ChiangJH, et al., 2020. Exosome-derived LINC00960 and LINC02470 promote the epithelial-mesenchymal transition and aggressiveness of bladder cancer cells. Cells, 9(6):1419.

[15]LiQ, WangHL, PengHR, et al., 2019. MicroRNAs: key players in bladder cancer. Mol Diagn Ther, 23(5):579-601.

[16]LiQ, HuyanT, CaiSN, et al., 2020. The role of exosomal miR-375-3p: a potential suppressor in bladder cancer via the Wnt/β-catenin pathway. FASEB J, 34(9):12177-12196.

[17]LiangZF, LuL, MaoJH, et al., 2017. Curcumin reversed chronic tobacco smoke exposure induced urocystic EMT and acquisition of cancer stem cells properties via Wnt/β-catenin. Cell Death Discov, 8(10):e3066.

[18]LinF, YinHB, LiXY, et al., 2020. Bladder cancer cell-secreted exosomal miR-21 activates the PI3K/AKT pathway in macrophages to promote cancer progression. Int J Oncol, 56(1):151-164.

[19]MeariniE, PoliG, CochettiG, et al., 2017. Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer. Onco Targets Ther, 10:2665-2673.

[20]MiyamotoDT, MouwKW, FengFY, et al., 2018. Molecular biomarkers in bladder preservation therapy for muscle-invasive bladder cancer. Lancet Oncol, 19(12):e683-e695.

[21]PantelK, Alix-PanabièresC, 2010. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med, 16(9):398-406.

[22]PegtelDM, GouldSJ, 2019. Exosomes. Annu Rev Biochem, 88:487-514.

[23]PoliG, BrancorsiniS, CochettiG, et al., 2015. Expression of inflammasome-related genes in bladder cancer and their association with cytokeratin 20 messenger RNA. Urol Oncol Semin Orig Invest, 33(12):505.e1-505.e7.

[24]PoliG, CochettiG, BoniA, et al., 2017. Characterization of inflammasome-related genes in urine sediments of patients receiving intravesical BCG therapy. Urol Oncol Semin Orig Invest, 35(12):674.e19-674.e24.

[25]PoliG, EgidiMG, CochettiG, et al., 2020. Relationship between cellular and exosomal miRNAs targeting NOD-like receptors in bladder cancer: preliminary results. Minerva Urol Nefrol, 72(2):207-213.

[26]Ringuette GouletC, BernardG, TremblayS, et al., 2018. Exosomes induce fibroblast differentiation into cancer-associated fibroblasts through TGFβ signaling. Mol Cancer Res, 16(7):1196-1204.

[27]SiegelRL, MillerKD, JemalA, 2019. Cancer statistics, 2019. CA Cancer J Clin, 69(1):7-34.

[28]StreetJM, YuenPST, StarRA, 2014. Bioactive exosomes: possibilities for diagnosis and management of bladder cancer. J Urol, 192(2):297-298.

[29]WangJS, YangK, YuanWX, et al., 2018. Determination of serum exosomal H19 as a noninvasive biomarker for bladder cancer diagnosis and prognosis. Med Sci Monit, 24:9307-9316.

[30]WuCH, SilversCR, MessingEM, et al., 2019. Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells. J Biol Chem, 294(9):3207-3218.

[31]XueM, ChenW, XiangA, et al., 2017. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1. Mol Cancer, 16:143.

[32]YazarlouF, MowlaSJ, Kholghi OskooeiV, et al., 2018a. Urine exosome gene expression of cancer-testis antigens for prediction of bladder carcinoma. Cancer Manage Res, 10:5373-5381.

[33]YazarlouF, ModarressiMH, MowlaSJ, et al., 2018b. Urinary exosomal expression of long non-coding RNAs as diagnostic marker in bladder cancer. Cancer Manage Res, 10:6357-6365.

[34]YinXB, ZhengXP, LiuM, et al., 2020. Exosomal miR-663b targets Ets2-repressor factor to promote proliferation and the epithelial-mesenchymal transition of bladder cancer cells. Cell Biol Int, 44(4):958-965.

[35]YoshidaK, TsudaM, MatsumotoR, et al., 2019. Exosomes containing ErbB2/CRK induce vascular growth in premetastatic niches and promote metastasis of bladder cancer. Cancer Sci, 110(7):2119-2132.

[36]ZhanY, DuLT, WangLS, et al., 2018. Expression signatures of exosomal long non-coding RNAs in urine serve as novel non-invasive biomarkers for diagnosis and recurrence prediction of bladder cancer. Mol Cancer, 17:142.

[37]ZhangSJ, DuLT, WangLS, et al., 2019. Evaluation of serum exosomal lncRNA-based biomarker panel for diagnosis and recurrence prediction of bladder cancer. J Cell Mol Med, 23(2):1396-1405.

[38]ZhengR, DuML, WangXW, et al., 2018. Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression. Mol Cancer, 17(1):143.