Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 7/2013

01.07.2013 | Original Paper

miR-708 promotes the development of bladder carcinoma via direct repression of Caspase-2

verfasst von: Tao Song, Xu Zhang, Lei Zhang, Jun Dong, Wei Cai, Jiangping Gao, Baofa Hong

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 7/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Bladder cancer is one of the world’s top ten malignant tumors. The crucial role of microRNA in carcinogenesis has been well emphasized. Considering miRNA expression was tumor stage-, tissue-, or even development-specific, more experimental evidences about the functions of miRNAs in bladder cancer should be discovered to advance applying of miRNA in the diagnosis or therapy of cancer.

Methods

MiR-708 level in bladder carcinoma and adjacent noncancerous tissues was tested by real-time qPCR. Cell apoptosis was analyzed by using flow cytometry. The tumorigenicity of bladder carcinoma cells was evaluated in nude mice model. Luciferase reporter gene assays were performed to identify the interaction between miR-708 and 3′UTR of Caspase-2 mRNA. The protein level of Caspase-2 was determined by western blotting.

Results

In this study, we reported that miR-708 was frequently dysregulated in human bladder carcinoma tissues compared to normal tissues. In addition, we found that silencing of miR-708 could promote the T24 and 5637 cells to apoptosis and inhibit the bladder tumor growth in vivo. Also, Caspase-2 was proved to be one of direct targets of miR-708 in T24 and 5637 cells. Further results showed that Caspase-2 was involved in the miR-708 regulated cell apoptosis.

Conclusions

All together, these results suggest miR-708 may act as an oncogene and induce the carcinogenicity of bladder cancer by down-regulating Caspase-2 level.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Alvarez A, Lokeshwar VB (2007) Bladder cancer biomarkers: current developments and future implementation. Curr Opin Urol 17(5):341–346PubMedCrossRef Alvarez A, Lokeshwar VB (2007) Bladder cancer biomarkers: current developments and future implementation. Curr Opin Urol 17(5):341–346PubMedCrossRef
Zurück zum Zitat Chen YH, Wang SQ, Wu XL, Shen M, Chen ZG, Chen XG, Liu YX, Zhu XL, Guo F, Duan XZ, Han XC, Tao ZH (2011) Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol Oncol. doi:10.1016/j.bbr.2011.03.031 Chen YH, Wang SQ, Wu XL, Shen M, Chen ZG, Chen XG, Liu YX, Zhu XL, Guo F, Duan XZ, Han XC, Tao ZH (2011) Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol Oncol. doi:10.​1016/​j.​bbr.​2011.​03.​031
Zurück zum Zitat Cookson MS, Herr HW, Zhang ZF, Soloway S, Sogani PC, Fair WR (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 158:62–67PubMedCrossRef Cookson MS, Herr HW, Zhang ZF, Soloway S, Sogani PC, Fair WR (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 158:62–67PubMedCrossRef
Zurück zum Zitat Esquela-Kerscher A, Slack FJ (2006) Oncomirs microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRef Esquela-Kerscher A, Slack FJ (2006) Oncomirs microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRef
Zurück zum Zitat Fendler A, Stephan C, Yousef GM, Jung K (2011) MicroRNAs as regulators of signal transduction in urological tumors. Clin Chem 57(7):954–968PubMedCrossRef Fendler A, Stephan C, Yousef GM, Jung K (2011) MicroRNAs as regulators of signal transduction in urological tumors. Clin Chem 57(7):954–968PubMedCrossRef
Zurück zum Zitat Green DR, Evan GI (2000) A matter of life and death. Nature 407(6805):802–809CrossRef Green DR, Evan GI (2000) A matter of life and death. Nature 407(6805):802–809CrossRef
Zurück zum Zitat Han BW, Feng DD, Li ZG, Luo XQ, Zhang H, Li XJ, Zhang XJ, Zheng LL, Zeng CW, Lin KY, Zhang P, Xu L, Chen YQ (2011) A set of miRNAs that involve in the pathways of drug resistance and leukemic stem-cell differentiation is associated with the risk of relapse and glucocorticoid response in childhood ALL. Hum Mol Genet 20(24):4903–4915PubMedCrossRef Han BW, Feng DD, Li ZG, Luo XQ, Zhang H, Li XJ, Zhang XJ, Zheng LL, Zeng CW, Lin KY, Zhang P, Xu L, Chen YQ (2011) A set of miRNAs that involve in the pathways of drug resistance and leukemic stem-cell differentiation is associated with the risk of relapse and glucocorticoid response in childhood ALL. Hum Mol Genet 20(24):4903–4915PubMedCrossRef
Zurück zum Zitat Herr HW (1997) Natural history of superficial bladder tumors: 10- to 20-year follow-up of treated patients. World J Urol 15:84–88PubMedCrossRef Herr HW (1997) Natural history of superficial bladder tumors: 10- to 20-year follow-up of treated patients. World J Urol 15:84–88PubMedCrossRef
Zurück zum Zitat Huang X, Yu HS, Chen Z, Li JL, Hu ZM, Gao JM (2010) A novel immunotherapy for superficial bladder cancer by the immobilization of streptavidin-tagged bioactive IL-2 on the biotinylated mucosal surface of the bladder wall. Chin J Cancer 29(6):611–616PubMedCrossRef Huang X, Yu HS, Chen Z, Li JL, Hu ZM, Gao JM (2010) A novel immunotherapy for superficial bladder cancer by the immobilization of streptavidin-tagged bioactive IL-2 on the biotinylated mucosal surface of the bladder wall. Chin J Cancer 29(6):611–616PubMedCrossRef
Zurück zum Zitat Imre G, Heering J, Takeda AN, Husmann M, Thiede B, zu Heringdorf DM, Green DR, van der Goot FG, Sinha B, Dötsch V, Rajalingam K (2012) Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis.The. EMBO J 31:2615–2628PubMedCrossRef Imre G, Heering J, Takeda AN, Husmann M, Thiede B, zu Heringdorf DM, Green DR, van der Goot FG, Sinha B, Dötsch V, Rajalingam K (2012) Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis.The. EMBO J 31:2615–2628PubMedCrossRef
Zurück zum Zitat Ismaili N, Amzerin M, Flechon A (2011) Chemotherapy in advanced bladder cancer: current status and future. J Hematol Oncol 4:35PubMedCrossRef Ismaili N, Amzerin M, Flechon A (2011) Chemotherapy in advanced bladder cancer: current status and future. J Hematol Oncol 4:35PubMedCrossRef
Zurück zum Zitat Jang JS, Jeon HS, Sun Z, Aubry MC, Tang H, Park CH, Rakhshan F, Schultz DA, Kolbert CP, Lupu R, Park JY, Harris CC, Yang P, Jen J (2012) Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers. Clin Cancer Res 18(13):3658–3667PubMedCrossRef Jang JS, Jeon HS, Sun Z, Aubry MC, Tang H, Park CH, Rakhshan F, Schultz DA, Kolbert CP, Lupu R, Park JY, Harris CC, Yang P, Jen J (2012) Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers. Clin Cancer Res 18(13):3658–3667PubMedCrossRef
Zurück zum Zitat Kim BM, Rode AB, Han EJ, Hong IS, Hong SH (2012) 5-Phenylselenyl- and 5-methylselenyl-methyl-2′-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells. Apoptosis 17(2):200–216PubMedCrossRef Kim BM, Rode AB, Han EJ, Hong IS, Hong SH (2012) 5-Phenylselenyl- and 5-methylselenyl-methyl-2′-deoxyuridine induce oxidative stress, DNA damage, and caspase-2-dependent apoptosis in cancer cells. Apoptosis 17(2):200–216PubMedCrossRef
Zurück zum Zitat Kitevska T, Spencer DM, Hawkins CJ (2009) Caspase-2: controversial killer or checkpoint controller? Apoptosis 14(7):829–848PubMedCrossRef Kitevska T, Spencer DM, Hawkins CJ (2009) Caspase-2: controversial killer or checkpoint controller? Apoptosis 14(7):829–848PubMedCrossRef
Zurück zum Zitat Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P (2007) Caspases in cell survival, proliferation and differentiation. Cell Death Differ 14(1):44–55PubMedCrossRef Lamkanfi M, Festjens N, Declercq W, Vanden Berghe T, Vandenabeele P (2007) Caspases in cell survival, proliferation and differentiation. Cell Death Differ 14(1):44–55PubMedCrossRef
Zurück zum Zitat Lee YS, Dutta A (2006) MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Investig Drugs 7(6):560–564PubMed Lee YS, Dutta A (2006) MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Investig Drugs 7(6):560–564PubMed
Zurück zum Zitat Li C, Feng Y, Coukos G (2009a) Therapeutic microRNA strategies in human cancer. AAPS J 11(4):747–757PubMedCrossRef Li C, Feng Y, Coukos G (2009a) Therapeutic microRNA strategies in human cancer. AAPS J 11(4):747–757PubMedCrossRef
Zurück zum Zitat Li S, Fu H, Wang Y, Tie Y, Xing R, Zhu J, Sun Z, Wei L, Zheng X (2009b) MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology 49(4):1194–1202PubMedCrossRef Li S, Fu H, Wang Y, Tie Y, Xing R, Zhu J, Sun Z, Wei L, Zheng X (2009b) MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology 49(4):1194–1202PubMedCrossRef
Zurück zum Zitat Lynam-Lennon N, Maher SG, Reynolds JV (2009) The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc 84:55–71PubMedCrossRef Lynam-Lennon N, Maher SG, Reynolds JV (2009) The roles of microRNA in cancer and apoptosis. Biol Rev Camb Philos Soc 84:55–71PubMedCrossRef
Zurück zum Zitat Muppani N, Nyman U, Joseph B (2011) TAp73alpha protects small cell lung carcinoma cells from caspase-2 induced mitochondrial mediated apoptotic cell death. Oncotarget 2(12):1145–1154PubMed Muppani N, Nyman U, Joseph B (2011) TAp73alpha protects small cell lung carcinoma cells from caspase-2 induced mitochondrial mediated apoptotic cell death. Oncotarget 2(12):1145–1154PubMed
Zurück zum Zitat Noguchi S, Mori T, Hoshino Y, Maruo K, Yamada N, Kitade Y, Naoe T, Akao Y (2011) MicroRNA-143 functions as a tumor suppressor in human bladder. Cancer Lett 307(2):211–220PubMedCrossRef Noguchi S, Mori T, Hoshino Y, Maruo K, Yamada N, Kitade Y, Naoe T, Akao Y (2011) MicroRNA-143 functions as a tumor suppressor in human bladder. Cancer Lett 307(2):211–220PubMedCrossRef
Zurück zum Zitat Papagiannakopoulos T, Kosik KS (2008) MicroRNAs: regulators of oncogenesis and stemness. BMC Med 6:15PubMedCrossRef Papagiannakopoulos T, Kosik KS (2008) MicroRNAs: regulators of oncogenesis and stemness. BMC Med 6:15PubMedCrossRef
Zurück zum Zitat Ren K, Lu J, Porollo A, Du C (2012) Tumor-suppressing function of caspase-2 requires catalytic site Cys-320 and site Ser-139 in mice. J Biol Chem 287(18):14792–14802PubMedCrossRef Ren K, Lu J, Porollo A, Du C (2012) Tumor-suppressing function of caspase-2 requires catalytic site Cys-320 and site Ser-139 in mice. J Biol Chem 287(18):14792–14802PubMedCrossRef
Zurück zum Zitat Saini S, Yamamura S, Majid S, Shahryari V, Hirata H, Tanaka Y, Dahiya R (2011) MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells. Cancer Res 71(19):6208–6219PubMedCrossRef Saini S, Yamamura S, Majid S, Shahryari V, Hirata H, Tanaka Y, Dahiya R (2011) MicroRNA-708 induces apoptosis and suppresses tumorigenicity in renal cancer cells. Cancer Res 71(19):6208–6219PubMedCrossRef
Zurück zum Zitat Saini S, Majid S, Shahryari V, Arora S, Yamamura S, Chang I, Zaman MS, Deng G, Tanaka Y, Dahiya R (2012) miRNA-708 control of CD44 + prostate cancer-initiating cells. Cancer Res 72(14):3618–3630PubMedCrossRef Saini S, Majid S, Shahryari V, Arora S, Yamamura S, Chang I, Zaman MS, Deng G, Tanaka Y, Dahiya R (2012) miRNA-708 control of CD44 + prostate cancer-initiating cells. Cancer Res 72(14):3618–3630PubMedCrossRef
Zurück zum Zitat Shelley MD, Wilt TJ, Barber J, Mason MD (2004) A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice. Clin Oncol 16:166–171CrossRef Shelley MD, Wilt TJ, Barber J, Mason MD (2004) A meta-analysis of randomised trials suggests a survival benefit for combined radiotherapy and radical cystectomy compared with radical radiotherapy for invasive bladder cancer: are these data relevant to modern practice. Clin Oncol 16:166–171CrossRef
Zurück zum Zitat Shenouda SK, Alahari SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28(3–4):369–378PubMedCrossRef Shenouda SK, Alahari SK (2009) MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev 28(3–4):369–378PubMedCrossRef
Zurück zum Zitat Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y, Dong J, Cai W, Li H (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev 11(4):905–911PubMed Song T, Xia W, Shao N, Zhang X, Wang C, Wu Y, Dong J, Cai W, Li H (2010) Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pac J Cancer Prev 11(4):905–911PubMed
Zurück zum Zitat Sudarshan S, Holman DH, Hyer ML, Voelkel-Johnson C, Dong JY, Norris JS (2005) In vitro efficacy of Fas ligand gene therapy for the treatment of bladder cancer. Cancer Gene Ther 12:12–18PubMedCrossRef Sudarshan S, Holman DH, Hyer ML, Voelkel-Johnson C, Dong JY, Norris JS (2005) In vitro efficacy of Fas ligand gene therapy for the treatment of bladder cancer. Cancer Gene Ther 12:12–18PubMedCrossRef
Zurück zum Zitat Tang Y, Wells JA, Arkin MR (2011) Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis. J Biol Chem 286(39):34147–34154PubMedCrossRef Tang Y, Wells JA, Arkin MR (2011) Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis. J Biol Chem 286(39):34147–34154PubMedCrossRef
Zurück zum Zitat Tiwari M, Lopez-Cruzan M, Morgan WW, Herman B (2011) Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J Biol Chem 286(10):8493–8506PubMedCrossRef Tiwari M, Lopez-Cruzan M, Morgan WW, Herman B (2011) Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J Biol Chem 286(10):8493–8506PubMedCrossRef
Zurück zum Zitat Trang P, Weidhaas JB, Slack FJ (2008) MicroRNAs as potential cancer therapeutics. Oncogene 27:S52–S57PubMedCrossRef Trang P, Weidhaas JB, Slack FJ (2008) MicroRNAs as potential cancer therapeutics. Oncogene 27:S52–S57PubMedCrossRef
Zurück zum Zitat Wang CC, Chiang YM, Kuo PL, Chang JK, Hsu YL (2008) Norsolorinic acid inhibits proliferation of T24 human bladder cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas/membrane-bound Fas ligand-mediated apoptotic pathway. Clin Exp Pharmacol Physiol 35:1301–1308PubMedCrossRef Wang CC, Chiang YM, Kuo PL, Chang JK, Hsu YL (2008) Norsolorinic acid inhibits proliferation of T24 human bladder cancer cells by arresting the cell cycle at the G0/G1 phase and inducing a Fas/membrane-bound Fas ligand-mediated apoptotic pathway. Clin Exp Pharmacol Physiol 35:1301–1308PubMedCrossRef
Zurück zum Zitat Wiklund ED, Bramsen JB, Hulf T, Dyrskjøt L, Ramanathan R, Hansen TB, Villadsen SB, Gao S, Ostenfeld MS, Borre M, Peter ME, Ørntoft TF, Kjems J, Clark SJ (2011) Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer 128(6):1327–1334PubMedCrossRef Wiklund ED, Bramsen JB, Hulf T, Dyrskjøt L, Ramanathan R, Hansen TB, Villadsen SB, Gao S, Ostenfeld MS, Borre M, Peter ME, Ørntoft TF, Kjems J, Clark SJ (2011) Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer 128(6):1327–1334PubMedCrossRef
Zurück zum Zitat Zhang B, Pan X, Cobb GP, Anderson TA (2007) MicroRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12PubMedCrossRef Zhang B, Pan X, Cobb GP, Anderson TA (2007) MicroRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12PubMedCrossRef
Metadaten
Titel
miR-708 promotes the development of bladder carcinoma via direct repression of Caspase-2
verfasst von
Tao Song
Xu Zhang
Lei Zhang
Jun Dong
Wei Cai
Jiangping Gao
Baofa Hong
Publikationsdatum
01.07.2013
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 7/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-013-1392-6

Weitere Artikel der Ausgabe 7/2013

Journal of Cancer Research and Clinical Oncology 7/2013 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.