Increased expression of TNFRSF14 indicates good prognosis and inhibits bladder cancer proliferation by promoting apoptosis

Zhu,Yu‑Di; Lu,Ming‑Yue

doi:10.3892/mmr.2018.9306

Increased expression of TNFRSF14 indicates good prognosis and inhibits bladder cancer proliferation by promoting apoptosis

Authors:
- Yu‑Di Zhu
- Ming‑Yue Lu
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Affiliations: Department of Urology, Ningbo No. 2 Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315010, P.R. China, Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
Published online on: July 23, 2018 https://doi.org/10.3892/mmr.2018.9306
Pages: 3403-3410

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Abstract

Despite advances in management, bladder cancer remains a principal cause of cancer‑associated complications. Tumor necrosis factor receptor superfamily member 14 (TNFRSF14) is dysregulated in certain types of cancer; however, limited data are available on the expression and function of TNFRSF14 in bladder cancer. In the present study, the aim was to evaluate the expression and biological functions of TNFRSF14 in bladder cancer. Firstly, the expression levels of TNFRSF14 in bladder cancer tissue were examined using The Cancer Genome Atlas (TCGA) database. Secondly, reverse transcription‑quantitative polymerase chain reaction was utilized to investigate the expression levels of TNFRSF14 in the T24, SW780 and EJ‑M3 bladder cancer cell lines. Transfection and Cell Counting kit‑8 (CCK‑8) assay was used to evaluate whether TNFRSF14 overexpression or silencing would have an effect on cell proliferation of T24 and EJ‑M3 cells. In addition, TNFRSF14‑induced apoptotic cells were identified using Annexin V‑fluorescein isothiocyanate and propidium iodide staining. Western blot analysis was used to detect proteins associated with the phosphatidylinositol 3‑kinase pathway. According to the TCGA dataset, the expression levels TNFRSF14 were decreased in bladder cancer tissue compared with in normal control samples. Patients with bladder cancer exhibiting low expression levels of TNFRSF14 had a worse prognosis compared to those with high expression levels of TNFRSF14. Overexpression of TNFRSF14 in T24 cells led to increased apoptosis and inhibited cell proliferation in vitro. Western blotting demonstrated that TNFRSF14 overexpression increased the expression levels of caspase3‑p17 in T24 cells, but significantly decreased the expression levels of phosphorylated (p)‑protein kinase B (AKT) and P70 S6 kinase (P70). TNFRSF14 silencing in EJ‑M3 cells enhanced cell growth, inhibited cell apoptosis, increased the expression levels of p‑AKT and P70, and decreased the expression levels of caspase3‑p17. In conclusion, TNFRSF14 may serve a tumor suppressive role in bladder cancer by inducing apoptosis and suppressing proliferation, and act as a novel prognostic biomarker for bladder cancer.

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1	Luo M, Li Z, Wang W, Zeng Y, Liu Z and Qiu J: Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett. 333:213–221. 2013. View Article : Google Scholar : PubMed/NCBI
2	Bo J, Yang G, Huo K, Jiang H, Zhang L, Liu D and Huang Y: microRNA-203 suppresses bladder cancer development by repressing bcl-w expression. FEBS J. 278:786–292. 2011. View Article : Google Scholar : PubMed/NCBI
3	Stein JP, Grossfeld GD, Ginsberg DA, Esrig D, Freeman JA, Figueroa AJ, Skinner DG and Cote RJ: Prognostic markers in bladder cancer: A contemporary review of the literature. J Urol. 160:645–659. 1998. View Article : Google Scholar : PubMed/NCBI
4	Laufer M, Ramalingam S, Schoenberg MP, Haisfieldwolf ME, Zuhowski EG, Trueheart IN, Eisenberger MA, Nativ O and Egorin MJ: Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: A phase I and pharmacokinetic study. J Clin Oncol. 21:697–703. 2003. View Article : Google Scholar : PubMed/NCBI
5	Shui JW, Steinberg MW and Kronenberg M: Regulation of inflammation, autoimmunity and infection immunity by HVEM-BTLA signaling. J Leukoc Biol. 89:517–523. 2011. View Article : Google Scholar : PubMed/NCBI
6	Bolyard C, Ji YY, Wang PY, Saini U, Rath KS, Cripe T, Zhang J, Selvendiran K and Kaur B: Doxorubicin synergizes with 34.5 ENVE to enhance antitumor efficacy against metastatic ovarian cancer. Clin Cancer Res. 20:6479–6494. 2014. View Article : Google Scholar : PubMed/NCBI
7	Shui JW, Larange A, Kim G, Vela JL, Zahner S, Cheroutre H and Kronenberg M: HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria. Nature. 488:222–225. 2012. View Article : Google Scholar : PubMed/NCBI
8	Salipante SJ, Adey A, Thomas A, Lee C, Liu YJ, Kumar A, Lewis AP, Wu D, Fromm JR and Shendure J: Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma. Genes Chromosomes Cancer. 55:278–287. 2016. View Article : Google Scholar : PubMed/NCBI
9	Kotsiou E, Okosun J, Besley C, Iqbal S, Matthews J, Fitzgibbon J, Gribben JG and Davies JK: TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses. Blood. 128:72–81. 2016. View Article : Google Scholar : PubMed/NCBI
10	Cheung KJ, Johnson NA, Affleck JG, Severson T, Steidl C, Ben-Neriah S, Schein J, Morin RD, Moore R, Shah SP, et al: Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis. Cancer Res. 70:9166–9174. 2010. View Article : Google Scholar : PubMed/NCBI
11	Cancer Genome Atlas Research Network: Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 507:315–322. 2014. View Article : Google Scholar : PubMed/NCBI
12	Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W and Smyth GK: Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43:e472015. View Article : Google Scholar : PubMed/NCBI
13	Capesdavis A, Theodosopoulos G, Atkin I, Drexler HG, Kohara A, MacLeod RA, Masters JR, Nakamura Y, Reid YA, Reddel RR and Freshney RI: Check your cultures! A list of cross-contaminated or misidentified cell lines. Int J Cancer. 127:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
14	Yang D, Wang H, Wang J, Zhang C and Xu H: Establishment of a fluorescent implantation metastasis model of bladder cancer and real-time microscopic detection in nude mice. Asian Pac J Cancer Prev. 12:393–396. 2011.PubMed/NCBI
15	Girnita A, All-Ericsson C, Economou MA, Astrom K, Axelson M, Seregard S, Larsson O and Girnita L: The insulin-like growth factor-I receptor inhibitor picropodophyllin causes tumor regression and attenuates mechanisms involved in invasion of uveal melanoma cells. Clin Cancer Res. 12:1383–1391. 2006. View Article : Google Scholar : PubMed/NCBI
16	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
17	Zhang X, Qi H, Wang S, Feng L, Ji Y, Tao L, Li S and Wei Y: Cellular responses of aniline oligomers: A preliminary study. Toxicol Res. 1:201–205. 2012. View Article : Google Scholar
18	van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, Witjes JA and Zlotta AR: Recurrence and progression of disease in non-muscle-invasive bladder cancer: From epidemiology to treatment strategy. Eur Urol. 56:430–442. 2009. View Article : Google Scholar : PubMed/NCBI
19	Geng W, Ng KTP, Sun CKW, Yau WL, Liu XB, Cheng Q, Poon RT, Lo CM, Man K and Fan ST: The role of proline rich tyrosine kinase 2(Pyk2) on cisplatin resistance in hepatocellular carcinoma. PLoS One. 6:e273622011. View Article : Google Scholar : PubMed/NCBI
20	Harrop JA, Mcdonnell PC, Brigham-Burke M, Lyn SD, Minton J, Tan KB, Dede K, Spampanato J, Silverman C, Hensley P, et al: Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth. J Biol Chem. 273:27548–27556. 1998. View Article : Google Scholar : PubMed/NCBI
21	Gaur U and Aggarwal BB: Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol. 66:1403–1408. 2003. View Article : Google Scholar : PubMed/NCBI
22	Hengartner MO: Biochemistry of apoptosis. Nature. 407:770–776. 2016. View Article : Google Scholar
23	Hail N Jr, Carter BZ, Konopleva M and Andreeff M: Apoptosis effector mechanisms: A requiem performed in different keys. Apoptosis. 11:889–904. 2006. View Article : Google Scholar : PubMed/NCBI
24	Hartmann A, Troadec J, Hunot S, Kikly K, Faucheux B, Mouatt-Prigent A, Ruberg M, Agid Y and Hirsch E: Caspase-8 is an effector in apoptotic death of dopaminergic neurons in parkinson's disease, but pathway inhibition results in neuronal necrosis. J Neurosci. 21:2247–2255. 2001. View Article : Google Scholar : PubMed/NCBI
25	Isabelle M, Moreel X, Gagné JP, Rouleau M, Ethier C, Gagné P, Hendzel MJ and Poirier GG: Investigation of PARP-1, PARP-2 and PARG interactomes by affinity-purification mass spectrometry. Proteome Sci. 8:222010. View Article : Google Scholar : PubMed/NCBI
26	Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI
27	Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 441:424–430. 2006. View Article : Google Scholar : PubMed/NCBI
28	Knowles MA, Platt FM, Ross RL and Hurst CD: Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer. Cancer Metastasis Rev. 28:305–316. 2009. View Article : Google Scholar : PubMed/NCBI
29	Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL and Arteaga CL: Phosphatidylinositol 3-kinase function is required for transforming growth factor β-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem. 275:368032000. View Article : Google Scholar : PubMed/NCBI
30	Mcconkey DJ, Choi W, Marquis L, Martin F, Williams MB, Shah J, Svatek R, Das A, Adam L, Kamat A, et al: Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 28:335–344. 2009. View Article : Google Scholar : PubMed/NCBI
31	Wang YB, Qin J, Zheng XY, Bai Y, Yang K and Xie LP: Diallyl trisulfide induces Bcl-2 and caspase-3-dependent apoptosis via downregulation of Akt phosphorylation in human T24 bladder cancer cells. Phytomedicine. 17:363–368. 2010. View Article : Google Scholar : PubMed/NCBI
32	Tang C, Lu YH, Xie JH, Wang F, Zou JN, Yang JS, Xing YY and Xi T: Downregulation of survivin and activation of caspase-3 through the PI3K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis. Anticancer Drugs. 20:249–258. 2009. View Article : Google Scholar : PubMed/NCBI