Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Inflammation Research
Published in: Inflammation Research 9/2021

01-09-2021 | Original Research Paper

Bladder mesenchymal stromal cell-derived exosomal miRNA-217 modulates bladder cancer cell survival through Hippo-YAP pathway

Authors: Zhong-Ming Huang, Hai Wang, Zhi-Gang Ji

Published in: Inflammation Research | Issue 9/2021

Login to get access

Abstract

Background

Donor cell-derived exosomes regulate recipient cell functions. The aim of this study was to investigate the effect of human normal bladder stromal cell (hBSC) derived exosomal miR-217 on bladder cell cancer proliferation and migration.

Methods

Human BSCs were transfected with miR-217 mimic or inhibitor and hBSC-derived exosomes were isolated. Human bladder cancer cell lines (T24 and 5367) were co-cultured with hBSC-derived exosomal miR-217 mimic or inhibitor. Proliferation, migration, and apoptosis of the bladder cancer cells were assessed by Edu assay, Transwell migration assay, and Annexin V assay.

Results

Expression of miR-217 was significantly higher in the T24 and 5367 cell lines (P < 0.01). Exosomal miR-217 mimic enhanced proliferation and migration of T24 and 5367 cells, but inhibited apoptosis of the cells (P < 0.01); in contrast, exosomal miR-217 inhibitor suppressed proliferation and migration but stimulated apoptosis of the two cancer cell lines (P < 0.01). Moreover, exosomal miR-217 mimic stimulated YAP and its target proteins including Cyr61, CTGF, and ANKRD1 (P < 0.01), and in contrast, exosomal miR-217 inhibitor suppressed YAP and its target proteins (P < 0.01).

Conclusion

These findings suggested that hBSC-derived exosomal miR-217 may act as oncogene in bladder cancer cells, and that Hippo-YAP signaling pathway maybe the target for miR-217 in the bladder cancer cell lines.
Literature
1.
2.
3.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.PubMedCrossRef
4.
Pang C, Guan Y, Li H, Chen W, Zhu G. Urologic cancer in China. Jpn J Clin Oncol. 2016;46:497–501.PubMedCrossRef
5.
Babjuk M, Burger M, Comperat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Roupret M, Shariat SF, Sylvester R, Zigeuner R, Capoun O, Cohen D, Escrig JLD, Hernandez V, Peyronnet B, Seisen T, Soukup V. European association of urology guidelines on non-muscle-invasive bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 update. Eur Urol. 2019;76:639–57.PubMedCrossRef
6.
Yin Z, Ren W. MicroRNA-217 acts as a tumor suppressor and correlates with the chemoresistance of cervical carcinoma to cisplatin. Onco Targets Ther. 2019;12:759–71.PubMedPubMedCentralCrossRef
7.
Akcakaya P, Ekelund S, Kolosenko I, Caramuta S, Ozata DM, Xie H, Lindforss U, Olivecrona H, Lui WO. miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer. Int J Oncol. 2011;39:311–8.PubMed
8.
Zou Q, Wu H, Fu F, Yi W, Pei L, Zhou M. RKIP suppresses the proliferation and metastasis of breast cancer cell lines through up-regulation of miR-185 targeting HMGA2. Arch Biochem Biophys. 2016;610:25–32.PubMedCrossRef
9.
Guo J, Feng Z, Huang Z, Wang H, Lu W. MicroRNA-217 functions as a tumour suppressor gene and correlates with cell resistance to cisplatin in lung cancer. Mol Cells. 2014;37:664–71.PubMedPubMedCentralCrossRef
10.
Xiao Y, Deng T, Su C, Shang Z. MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS. Oncol Lett. 2017;13:4986–94.PubMedPubMedCentralCrossRef
11.
Dong J, Wang M, Ni D, Zhang L, Wang W, Cui X, Fu S, Yao S. MicroRNA-217 functions as a tumor suppressor in cervical cancer cells through targeting Rho-associated protein kinase 1. Oncol Lett. 2018;16:5535–42.PubMedPubMedCentral
12.
13.
Agbaje JO, Heijsters G, Salem AS, Van Slycke S, Schepers S, Politis C, Vrielinck L. Coronectomy of deeply impacted lower third molar: incidence of outcomes and complications after One year follow-up. J Oral Maxillofac Res. 2015;6:e1.PubMedPubMedCentralCrossRef
14.
Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinform. 2015;13:17–24.CrossRef
15.
Dilsiz N. Role of exosomes and exosomal microRNAs in cancer. Future Sci OA. 2020;6:FSO65.
16.
Sun Z, Shi K, Yang S, Liu J, Zhou Q, Wang G, Song J, Li Z, Zhang Z, Yuan W. Effect of exosomal miRNA on cancer biology and clinical applications. Mol Cancer. 2018;17:147.PubMedPubMedCentralCrossRef
17.
Cochetti G, Rossi de Vermandois JA, Maula V, Giulietti M, Cecati M, Del Zingaro M, Cagnani R, Suvieri C, Paladini A, Mearini E. Role of miRNAs in prostate cancer: do we really know everything? Urol Oncol. 2020;38:623–35.PubMedCrossRef
18.
Poli G, Egidi MG, Cochetti G, Brancorsini S, Mearini E. Relationship between cellular and exosomal miRNAs targeting NOD-like receptors in bladder cancer: preliminary results. Minerva Urol Nefrol. 2020;72:207–13.PubMedCrossRef
19.
Cochetti G, Poli G, Guelfi G, Boni A, Egidi MG, Mearini E. Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: evaluation of potential diagnostic and prognostic role. Onco Targets Ther. 2016;9:7545–53.PubMedPubMedCentralCrossRef
20.
21.
Guelfi G, Cochetti G, Stefanetti V, Zampini D, Diverio S, Boni A, Mearini E. Next generation sequencing of urine exfoliated cells: an approach of prostate cancer microRNAs research. Sci Rep. 2018;8:7111.PubMedPubMedCentralCrossRef
22.
Mearini E, Poli G, Cochetti G, Boni A, Egidi MG, Brancorsini S. Expression of urinary miRNAs targeting NLRs inflammasomes in bladder cancer. Onco Targets Ther. 2017;10:2665–73.PubMedPubMedCentralCrossRef
23.
Thompson BJ. YAP/TAZ: drivers of tumor growth, metastasis, and resistance to therapy. BioEssays. 2020;42:e1900162.PubMedCrossRef
24.
Walko G, Woodhouse S, Pisco AO, Rognoni E, Liakath-Ali K, Lichtenberger BM, Mishra A, Telerman SB, Viswanathan P, Logtenberg M, Renz LM, Donati G, Quist SR, Watt FM. A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells. Nat Commun. 2017;8:14744.PubMedPubMedCentralCrossRef
25.
Muramatsu T, Imoto I, Matsui T, Kozaki K, Haruki S, Sudol M, Shimada Y, Tsuda H, Kawano T, Inazawa J. YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis. 2011;32:389–98.PubMedCrossRef
26.
Hiemer SE, Zhang L, Kartha VK, Packer TS, Almershed M, Noonan V, Kukuruzinska M, Bais MV, Monti S, Varelas X. A YAP/TAZ-regulated molecular signature is associated with oral squamous cell carcinoma. Mol Cancer Res. 2015;13:957–68.PubMedPubMedCentralCrossRef
27.
Grzeszkiewicz TM, Lindner V, Chen N, Lam SC, Lau LF. The angiogenic factor cysteine-rich 61 (CYR61, CCN1) supports vascular smooth muscle cell adhesion and stimulates chemotaxis through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans. Endocrinology. 2002;143:1441–50.PubMedCrossRef
28.
Lin MT, Chang CC, Chen ST, Chang HL, Su JL, Chau YP, Kuo ML. Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-kappaB-dependent XIAP up-regulation. J Biol Chem. 2004;279:24015–23.PubMedCrossRef
29.
Yang R, Chen Y, Chen D. Biological functions and role of CCN1/Cyr61 in embryogenesis and tumorigenesis in the female reproductive system (Review). Mol Med Rep. 2018;17:3–10.PubMed
30.
Li ZQ, Wu WR, Zhao C, Zhao C, Zhang XL, Yang Z, Pan J, Si WK. CCN1/Cyr61 enhances the function of hepatic stellate cells in promoting the progression of hepatocellular carcinoma. Int J Mol Med. 2018;41:1518–28.PubMed
31.
Sun ZJ, Wang Y, Cai Z, Chen PP, Tong XJ, Xie D. Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells. Br J Cancer. 2008;99:1656–67.PubMedPubMedCentralCrossRef
32.
Babic AM, Kireeva ML, Kolesnikova TV, Lau LF. CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth. Proc Natl Acad Sci U S A. 1998;95:6355–60.PubMedPubMedCentralCrossRef
33.
Yang L, Wu XH, Wang D, Luo CL, Chen LX. Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol Med Rep. 2013;8:1272–8.PubMedCrossRef
34.
Wang B, Shen ZL, Jiang KW, Zhao G, Wang CY, Yan YC, Yang Y, Zhang JZ, Shen C, Gao ZD, Ye YJ, Wang S. MicroRNA-217 functions as a prognosis predictor and inhibits colorectal cancer cell proliferation and invasion via an AEG-1 dependent mechanism. BMC Cancer. 2015;15:437.PubMedPubMedCentralCrossRef
35.
Sun B, Yang M, Li M, Wang F. The microRNA-217 functions as a tumor suppressor and is frequently downregulated in human osteosarcoma. Biomed Pharmacother. 2015;71:58–63.PubMedCrossRef
36.
Wang H, Dong X, Gu X, Qin R, Jia H, Gao J. The MicroRNA-217 functions as a potential tumor suppressor in gastric cancer by targeting GPC5. PLoS ONE. 2015;10:e0125474.PubMedPubMedCentralCrossRef
37.
Chen DL, Zhang DS, Lu YX, Chen LZ, Zeng ZL, He MM, Wang FH, Li YH, Zhang HZ, Pelicano H, Zhang W, Xu RH. microRNA-217 inhibits tumor progression and metastasis by downregulating EZH2 and predicts favorable prognosis in gastric cancer. Oncotarget. 2015;6:10868–79.PubMedPubMedCentralCrossRef
38.
Lu J, Zhu LF, Cai YM, Dong HY, Zhu L, Tan JM. Isolation and multipotential differentiation of mesenchymal stromal celllike progenitor cells from human bladder. Mol Med Rep. 2019;19:187–94.PubMedCrossRef
39.
Lobb RJ, Becker M, Wen SW, Wong CS, Wiegmans AP, Leimgruber A, Moller A. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles. 2015;4:27031.PubMedCrossRef
40.
Filipe V, Hawe A, Jiskoot W. Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010;27:796–810.PubMedPubMedCentralCrossRef
41.
Turley SJ, Cremasco V, Astarita JL. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol. 2015;15:669–82.PubMedCrossRef
42.
43.
Tkach M, Thery C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–32.PubMedCrossRef
44.
Schober JM, Chen N, Grzeszkiewicz TM, Jovanovic I, Emeson EE, Ugarova TP, Ye RD, Lau LF, Lam SC. Identification of integrin alpha(M)beta(2) as an adhesion receptor on peripheral blood monocytes for Cyr61 (CCN1) and connective tissue growth factor (CCN2): immediate-early gene products expressed in atherosclerotic lesions. Blood. 2002;99:4457–65.PubMedCrossRef
45.
Chen CC, Chen N, Lau LF. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem. 2001;276:10443–52.PubMedCrossRef
46.
Borkham-Kamphorst E, Steffen BT, Van de Leur E, Haas U, Tihaa L, Friedman SL, Weiskirchen R. CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis. Cell Signal. 2016;28:34–42.PubMedCrossRef
47.
You JJ, Yang CH, Yang CM, Chen MS. Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin alphanubeta3, FAK, PI3K/Akt, and NF-kappaB pathways in retinal vascular endothelial cells. Cell Signal. 2014;26:133–40.PubMedCrossRef
48.
Matika CA, Wasilewski M, Arnott JA, Planey SL. Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells. Mol Biol Cell. 2012;23:1976–85.PubMedPubMedCentralCrossRef
49.
Wang X, Xu T, Gao F, He H, Zhu Y, Shen Z. Targeting of CCN2 suppresses tumor progression and improves chemo-sensitivity in urothelial bladder cancer. Oncotarget. 2017;8:66316–27.PubMedPubMedCentralCrossRef
50.
Zanconato F, Cordenonsi M, Piccolo S. YAP and TAZ: a signalling hub of the tumour microenvironment. Nat Rev Cancer. 2019;19:454–64.PubMedCrossRef
51.
52.
Martin K, Pritchett J, Llewellyn J, Mullan AF, Athwal VS, Dobie R, Harvey E, Zeef L, Farrow S, Streuli C, Henderson NC, Friedman SL, Hanley NA, Piper HK. PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis. Nat Commun. 2016;7:12502.PubMedPubMedCentralCrossRef
53.
54.
Dong L, Lin F, Wu W, Liu Y, Huang W. Verteporfin inhibits YAP-induced bladder cancer cell growth and invasion via Hippo signaling pathway. Int J Med Sci. 2018;15:645–52.PubMedPubMedCentralCrossRef
55.
Ciamporcero E, Shen H, Ramakrishnan S, Yu KuS, Chintala S, Shen L, Adelaiye R, Miles KM, Ullio C, Pizzimenti S, Daga M, Azabdaftari G, Attwood K, Johnson C, Zhang J, Barrera G, Pili R. YAP activation protects urothelial cell carcinoma from treatment-induced DNA damage. Oncogene. 2016;35:1541–53.PubMedCrossRef
Metadata
Title
Bladder mesenchymal stromal cell-derived exosomal miRNA-217 modulates bladder cancer cell survival through Hippo-YAP pathway
Authors
Zhong-Ming Huang
Hai Wang
Zhi-Gang Ji
Publication date
01-09-2021
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 9/2021
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-021-01494-7

Other articles of this Issue 9/2021

Inflammation Research 9/2021 Go to the issue

Letter to the Editor

Acute reduction of visual acuity and visual field after Pfizer-BioNTech COVID-19 vaccine 2nd dose: a case report

Original Research Paper

TREM-1 aggravates chronic obstructive pulmonary disease development via activation NLRP3 inflammasome-mediated pyroptosis

Short Communication

A case of reactivation of varicella–zoster virus after BNT162b2 vaccine second dose?

Original Research Paper

Blockade of macrophage-associated programmed death 1 inhibits the pyroptosis signalling pathway in sepsis

Review

A spotlight on underlying the mechanism of AMPK in diabetes complications

Original Research Paper

Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits