miR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells

Fu,Bin; Wang,Yibing; Zhang,Xiali; Lang,Bin; Zhou,Xiaocheng; Xu,Xiaoyuan; Zeng,Tao; Liu,Weipeng; Zhang,Xu; Guo,Ju; Wang,Gongxian

doi:10.3892/ijo.2015.2837

miR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells

Authors:
- Bin Fu
- Yibing Wang
- Xiali Zhang
- Bin Lang
- Xiaocheng Zhou
- Xiaoyuan Xu
- Tao Zeng
- Weipeng Liu
- Xu Zhang
- Ju Guo
- Gongxian Wang
View Affiliations

Affiliations: Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China, Department of Laboratory Animal Science, Nanchang University, Nanchang 330006, P.R. China, School of Health Sciences, Macao Polytechnic Institute, Macao 999078, P.R. China, Key Laboratory of System Bio-medicine of Jiangxi Province, Medical College of Jiujiang University, Jiangxi, Jiujiang 332000, P.R. China, Jiangxi Provincil People's Hospital, Nanchang 330006, P.R. China, Department of Urology, Chinese PLA General Hospital, Beijing 100039, P.R. China
Published online on: January 13, 2015 https://doi.org/10.3892/ijo.2015.2837
Pages: 1169-1180

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Immune evasion of cancer cells is mainly due to the impaired transduction of apoptotic signals from immune cells to cancer cells, as well as inhibition of subsequent apoptosis signal cascades within the cancer cells. Over the past few decades, the research has focused more on the impaired transduction of the apoptotic signal from immune cells to cancer cells, rather than inhibition of the intracellular signaling pathways. In this study, miR‑221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR‑221. As a result, the repression of miR‑221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and VEGF-C were reduced, resulting in reduced invasiveness and infiltration capability of bladder cancer cells, thereby inhibiting the immune evasion of bladder cancer cells.

View Figures

View References

1	Abedinpour P, Baron VT, Welsh J, et al: Regression of prostate tumors upon combination of hormone ablation therapy and celecoxib in vivo. Prostate. 71:813–823. 2011. View Article : Google Scholar : PubMed/NCBI
2	Ahmad A, Aboukameel A, Kong DJ, et al: Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells. Cancer Res. 71:3400–3409. 2011. View Article : Google Scholar : PubMed/NCBI
3	Akkoc A, Inan S and Sonmez G: Matrix metalloproteinase (MMP-2 and MMP-9) and steroid receptor expressions in feline mammary tumors. Biotech Histochem. 87:312–319. 2012. View Article : Google Scholar : PubMed/NCBI
4	Amente S, Zhang J, Lavadera ML, et al: Myc and PI3K/AKT signaling cooperatively repress FOXO3a-dependent PUMA and GADD45a gene expression. Nucleic Acids Res. 39:9498–9507. 2011. View Article : Google Scholar : PubMed/NCBI
5	Asirvatham AJ, Gregorie CJ, Hu Z, et al: MicroRNA targets in immune genes and the Dicer/Argonaute and ARE machinery components. Mol Immunol. 45:1995–2006. 2008. View Article : Google Scholar
6	Bean GR, Ganesan YT, Dong YY, et al: PUMA and BIM are required for oncogene inactivation-induced apoptosis. Sci Signal. 6:ra202013.PubMed/NCBI
7	Campone M, Noel B, Couriaud C, et al: c-Myc dependent expression of proapoptotic Bim renders HER2-overexpressing breast cancer cells dependent on anti-apoptotic Mcl-1. Mol Cancer. 10:1102011. View Article : Google Scholar
8	Catto JW, Alcaraz A, Bjartell AS, et al: MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 59:671–681. 2011. View Article : Google Scholar : PubMed/NCBI
9	Chang LY, Lin YC, Mahalingam J, et al: Tumor-derived chemokine CCL5 enhances TGF-beta-mediated killing of CD8(+) T cells in colon cancer by T-regulatory cells. Cancer Res. 72:1092–1102. 2012. View Article : Google Scholar : PubMed/NCBI
10	Chen L, Zhang J, Han L, et al: Downregulation of miR-221/222 sensitizes glioma cells to temozolomide by regulating apoptosis independently of p53 status. Oncol Rep. 27:854–860. 2012.
11	Chopin D, Barei-Moniri R, Maille P, et al: Human urinary bladder transitional cell carcinomas acquire the functional Fas ligand during tumor progression. Am J Pathol. 162:1139–1149. 2003. View Article : Google Scholar : PubMed/NCBI
12	Di Martino MT, Gulla A, Cantafio ME, et al: In vitro and in vivo antitumor activity of miR-221/222 inhibitors in multiple myeloma. Oncotarget. 4:242–255. 2013.PubMed/NCBI
13	Eissa S, Badr S, Elhamid SA, et al: The value of combined use of survivin mRNA and matrix metalloproteinase 2 and 9 for bladder cancer detection in voided urine. Dis Markers. 34:57–62. 2013. View Article : Google Scholar :
14	Eissa S, Shabayek MI, Ismail MF, et al: Diagnostic evaluation of apoptosis inhibitory gene and tissue inhibitor matrix metalloproteinase-2 in patients with bladder cancer. IUBMB Life. 62:394–399. 2010.PubMed/NCBI
15	Errami Y, Naura AS, Kim H, et al: Apoptotic DNA fragmentation may be a cooperative activity between caspase-activated deoxy-ribonuclease and the poly(ADP-ribose) polymerase-regulated DNAS1L3, an endoplasmic reticulum-localized endonuclease that translocates to the nucleus during apoptosis. J Biol Chem. 288:3460–3468. 2013. View Article : Google Scholar :
16	Follis AV, Chipuk JE, Fisher JC, et al: PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nat Chem Biol. 9:163–168. 2013. View Article : Google Scholar : PubMed/NCBI
17	Foster RR, Satchell SC, Seckley J, et al: VEGF-C promotes survival in podocytes. Am J Physiol Renal Physiol. 291:F196–F207. 2006. View Article : Google Scholar : PubMed/NCBI
18	Garcia-Lora A, Algarra I and Garrido F: MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol. 195:346–355. 2003. View Article : Google Scholar : PubMed/NCBI
19	Gottardo F, Liu CG, Ferracin M, et al: Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 25:387–392. 2007. View Article : Google Scholar : PubMed/NCBI
20	Holoch PA and Griffith TS: TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. Eur J Pharmacol. 625:63–72. 2009. View Article : Google Scholar : PubMed/NCBI
21	Igney FH and Krammer PH: Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leukoc Biol. 71:907–920. 2002.PubMed/NCBI
22	Inman BA, Sebo TJ, Frigola X, et al: PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 109:1499–1505. 2007. View Article : Google Scholar : PubMed/NCBI
23	Jayasinghe C, Simiantonaki N, Michel-Schmidt R, et al: Endothelial VEGFR-3 expression in colorectal carcinomas is associated with hematogenous metastasis. Oncol Rep. 22:1093–1100. 2009. View Article : Google Scholar : PubMed/NCBI
24	Jayasooriya RG, Choi YH, Moon SK, et al: Methanol extract of Hydroclathrus clathratus suppresses matrix metalloproteinase-9 in T24 bladder carcinoma cells by suppressing the NF-kappaB and MAPK pathways. Oncol Rep. 27:541–546. 2012.
25	Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
26	Jin X, Xiao LJ, Zhang XS, et al: Apotosis in ovary. Front Biosci (Schol Ed). 3:680–697. 2011. View Article : Google Scholar
27	Kajiya K, Sawane M, Huggenberger R, et al: Activation of the VEGFR-3 pathway by VEGF-C attenuates UVB-induced edema formation and skin inflammation by promoting lymphangiogenesis. J Invest Dermatol. 129:1292–1298. 2009. View Article : Google Scholar
28	Khong HT and Restifo NP: Natural selection of tumor variants in the generation of ‘tumor escape’ phenotypes. Nat Immunol. 3:999–1005. 2002. View Article : Google Scholar : PubMed/NCBI
29	Krebs R, Tikkanen JM, Ropponen JO, et al: VEGF-C/VEGFR-3 signaling regulates inflammatory response in development of obliterative airway disease. J Heart Lung Transpl. 30:S1182011. View Article : Google Scholar
30	Langers AMJ, Verspaget HW, Hawinkels LJAC, et al: MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br J Cancer. 106:1495–1498. 2012. View Article : Google Scholar : PubMed/NCBI
31	Li XQ, Dang XG and Sun XB: Expression of survivin and VEGF-C in breast cancer tissue and its relation to lymphatic metastasis. Eur J Gynaecol Oncol. 33:178–182. 2012.PubMed/NCBI
32	Li Y, Yang K, Mao Q, et al: Inhibition of TGF-beta receptor I by siRNA suppresses the motility and invasiveness of T24 bladder cancer cells via modulation of integrins and matrix metallopro-teinase. Int Urol Nephrol. 42:315–323. 2010. View Article : Google Scholar
33	Lund AW, Duraes FV, Hirosue S, et al: VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 1:191–199. 2012. View Article : Google Scholar : PubMed/NCBI
34	Martins SF, Garcia EA, Luz MA, et al: Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer. Cancer Genomics Proteomics. 10:55–67. 2013.PubMed/NCBI
35	Min Y, Ghose S, Boelte K, et al: C/EBP-delta regulates VEGF-C autocrine signaling in lymphangiogenesis and metastasis of lung cancer through HIF-1 alpha. Oncogene. 30:4901–4909. 2011. View Article : Google Scholar : PubMed/NCBI
36	Neal MD, Sodhi CP, Jia H, et al: The P53 upregulated modulator of apoptosis (Puma) regulates Tlr4-mediated enterocyte apopotosis in the pathogenesis of necrotizing enterocolitis. Shock. 35:60. 2011.
37	Newton MR, Askeland EJ, Andresen ED, et al: Anti-interleukin-10R1 monoclonal antibody in combination with BCG is protective against bladder cancer metastasis in a murine orthotopic tumor model and demonstrates systemic specific antitumor immunity. Clin Exp Immunol. 177:261–268. 2014. View Article : Google Scholar : PubMed/NCBI
38	Niederkorn JY: Immune escape mechanisms of intraocular tumors. Prog Retin Eye Res. 28:329–347. 2009. View Article : Google Scholar : PubMed/NCBI
39	Okada A: Roles of matrix metalloproteinases and tissue inhibitor of metalloproteinase (TIMP) in cancer invasion and metastasis. Gan To Kagaku Ryoho. 26:2247–2252. 1999.
40	Okada R, Nagaosa K, Kuraishi T, et al: Apoptosis-dependent externalization and involvement in apoptotic cell clearance of DmCaBP1, an endoplasmic reticulum protein of Drosophila. J Biol Chem. 287:3138–3146. 2012. View Article : Google Scholar :
41	Olofsson B, Jeltsch M, Eriksson U, et al: Current biology of VEGF-B and VEGF-C. Curr Opin Biotech. 10:528–535. 1999. View Article : Google Scholar : PubMed/NCBI
42	Piazzolla G, Nuzzaci M, Vitti A, et al: Apoptotic effects of a chimeric plant virus carrying a mimotope of the hepatitis C virus hypervariable region 1: role of caspases and endoplasmic reticulum-stress. J Clin Immunol. 32:866–876. 2012. View Article : Google Scholar : PubMed/NCBI
43	Planaguma L, Liljestrom M, Alameda F, et al: Matrix metalloproteinase-2 and matrix metalloproteinase-9 codistribute with transcription factors RUNX1/AML1 and ETV5/ERM at the invasive front of endometrial and ovarian carcinoma. Hum Pathol. 42:57–67. 2011. View Article : Google Scholar
44	Poyet C, Banzola I, Linto T, et al: Bladder cancer micro-environment influences maturation signature in lymphatic endothelial cells (LECs) by VEGF-C. Eur Urol (Suppl). 11:E906–U905. 2012. View Article : Google Scholar
45	Rabinovich GA, Gabrilovich D and Sotomayor EM: Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 25:267–296. 2007. View Article : Google Scholar
46	Saharinen P, Eklund L, Pulkki K, et al: VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 17:347–362. 2011. View Article : Google Scholar : PubMed/NCBI
47	Sato H, Takino T and Miyamori H: Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer Sci. 96:212–217. 2005. View Article : Google Scholar : PubMed/NCBI
48	Seiler R, Thalmann GN and Fleischmann A: MMP-2 and MMP-9 in lymph-node-positive bladder cancer. J Clin Pathol. 64:1078–1082. 2011. View Article : Google Scholar : PubMed/NCBI
49	Senger DR, Van de Water L, Brown LF, et al: Vascular permeability factor (VPF, VEGF) in tumor biology. Cancer Metastasis Rev. 12:303–324. 1993. View Article : Google Scholar : PubMed/NCBI
50	Siddle H, Kreiss A, Tovab C, et al: Immune escape strategies of a contagious cancer, devil facial tumour disease. Mol Immunol. 51:302012. View Article : Google Scholar
51	Siriwardena BSMS, Kudo Y, Ogawa I, et al: VEGF-C is associated with lymphatic status and invasion in oral cancer. J Clin Pathol. 61:103–108. 2008. View Article : Google Scholar
52	Stanton MJ, Dutta S, Zhang H, et al: Autophagy control by the VEGF-C/NRP-2 axis in cancer and its implication for treatment resistance. Cancer Res. 73:160–171. 2013. View Article : Google Scholar :
53	Sullu Y, Demirag GG, Yildirim A, et al: Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast. Pathol Res Pract. 207:747–753. 2011. View Article : Google Scholar : PubMed/NCBI
54	Takano S: Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation. Brain Tumor Pathol. 29:73–86. 2012. View Article : Google Scholar : PubMed/NCBI
55	Takizawa H, Kondo K, Fujino H, et al: The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer. Br J Cancer. 95:75–79. 2006. View Article : Google Scholar : PubMed/NCBI
56	Torii A, Kodera Y, Ito M, et al: Matrix metalloproteinase 9 in mucosally invasive gastric cancer. Gastric Cancer. 1:142–145. 1998. View Article : Google Scholar
57	Tsubata T: Apotosis of mature B cells. Int Rev Immunol. 18:347–365. 1999. View Article : Google Scholar
58	Valtola R, Salven P, Heikkila P, et al: VEGFR-3 and its ligand VEGF-C are associated with angiogenesis in breast cancer. Am J Pathol. 154:1381–1390. 1999. View Article : Google Scholar : PubMed/NCBI
59	Vasala K, Paakko P and Turpeenniemi-Hujanen T: Matrix metalloproteinase-9 (MMP-9) immunoreactive protein in urinary bladder cancer: a marker of favorable prognosis. Anticancer Res. 28:1757–1761. 2008.PubMed/NCBI
60	Vasala K and Turpeenniemi-Hujanen T: Serum tissue inhibitor of metalloproteinase-2 (TIMP-2) and matrix metalloproteinase-2 in complex with the inhibitor (MMP-2:TIMP-2) as prognostic markers in bladder cancer. Clin Biochem. 40:640–644. 2007. View Article : Google Scholar : PubMed/NCBI
61	Wang F, Li HM, Wang HP, et al: siRNA-mediated knockdown of VEGF-A, VEGF-C and VEGFR-3 suppresses the growth and metastasis of mouse bladder carcinoma in vivo. Exp Ther Med. 1:899–904. 2010.PubMed/NCBI
62	Wang Z, Li R, Zhou B, et al: Relationships of human laryngeal squamous cell carcinomas with the expression of VEGF-C and VEGFR-3. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 26:842–846. 2009.(In Chinese). PubMed/NCBI
63	Wu K, Wang X, Xie Z, et al: Glutathione S-transferase P1 gene polymorphism and bladder cancer susceptibility: an updated analysis. Mol Biol Rep. 40:687–695. 2013. View Article : Google Scholar
64	Yerlikaya A, Okur E and Ulukaya E: The p53-independent induction of apoptosis in breast cancer cells in response to proteasome inhibitor bortezomib. Tumor Biol. 33:1385–1392. 2012. View Article : Google Scholar
65	Yonemura Y, Fushida S, Bando E, et al: Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer. Eur J Cancer. 37:918–923. 2001. View Article : Google Scholar : PubMed/NCBI
66	Yu J and Zhang L: No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell. 4:248–249. 2003. View Article : Google Scholar : PubMed/NCBI
67	Yu J, Zhang L, Hwang PM, et al: PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell. 7:673–682. 2001. View Article : Google Scholar : PubMed/NCBI
68	Zhang C, Zhang J, Zhang A, et al: PUMA is a novel target of miR-221/222 in human epithelial cancers. Int J Oncol. 37:1621–1626. 2010.PubMed/NCBI
69	Zhang CZ, Zhang JX, Zhang AL, et al: MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer. 9:2292010. View Article : Google Scholar : PubMed/NCBI
70	Zhang LN, Li JY and Xu W: A review of the role of Puma, Noxa and Bim in the tumorigenesis, therapy and drug resistance of chronic lymphocytic leukemia. Cancer Gene Ther. 20:1–7. 2013. View Article : Google Scholar
71	Zhao ZW, Wang JJ, Tang JS, et al: JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells. Biochem J. 444:291–301. 2012. View Article : Google Scholar : PubMed/NCBI
72	Zheng M, Zhang Q, Joe Y, et al: Curcumin induces apoptotic cell death of activated human CD4⁺ T cells via increasing endoplasmic reticulum stress and mitochondrial dysfunction. Int Immunopharmacol. 15:517–523. 2013. View Article : Google Scholar : PubMed/NCBI
73	Zhu X, Tai W, Shi W, et al: Matrix metalloproteinase-9 silencing by RNA interference promotes the adhesive-invasive switch in HT1080 human fibrosarcoma cells. Clin Lab. 58:313–322. 2012.PubMed/NCBI
74	Nakano K and Vousden KH: PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell. 7:683–694. 2001. View Article : Google Scholar : PubMed/NCBI