| |
MiR-181b sensitizes glioma cells to teniposide by targeting MDM2
- 作者：Yan-chang Sun ; Jing Wang ; Cheng-cheng Guo ; Ke Sai ; Jian Wang ; Fu-rong Chen…
- 关键词：miR ; 181b ; Teniposide ; Glioma ; Mouse double minute 2 homolog (MDM2)
- 刊名：BMC Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：14
- 期：1
- 全文大小：920 KB
- 参考文献：1. Dunn, GP, Rinne, ML, Wykosky, J, Genovese, G, Quayle, SN, Dunn, IF, Agarwalla, PK, Chheda, MG, Campos, B, Wang, A, Brennan, C, Ligon, KL, Furnari, F, Cavenee, WK, Depinho, RA, Chin, L, Hahn, WC (2012) Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev 26: pp. 756-784 CrossRef
2. Wen, PY, Lee, EQ, Reardon, DA, Ligon, KL, Alfred Yung, WK (2012) Current clinical development of PI3K pathway inhibitors in glioblastoma. Neuro Oncol 14: pp. 819-829 CrossRef
Cancer facts and figures 2013. American Cancer Society, Atlanta, GA
3. Stupp, R, Hegi, ME, Mason, WP, van den Bent, MJ, Taphoorn, MJ, Janzer, RC, Ludwin, SK, Allgeier, A, Fisher, B, Belanger, K, Hau, P, Brandes, AA, Gijtenbeek, J, Marosi, C, Vecht, CJ, Mokhtari, K, Wesseling, P, Villa, S, Eisenhauer, E, Gorlia, T, Weller, M, Lacombe, D, Cairncross, JG, Mirimanoff, RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10: pp. 459-466 CrossRef
4. Mirimanoff, RO (2014) High-grade gliomas: reality and hopes. Chin J Cancer 33: pp. 1-3 CrossRef
5. Qiu, ZK, Shen, D, Chen, YS, Yang, QY, Guo, CC, Feng, BH, Chen, ZP (2013) Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells. Chin J Cancer 33: pp. 115-122 CrossRef
6. Esquela-Kerscher, A, Slack, FJ (2006) Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 6: pp. 259-269 CrossRef
7. Shi, L, Cheng, Z, Zhang, J, Li, R, Zhao, P, Fu, Z, You, Y (2008) hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res 1236: pp. 185-193 CrossRef
8. Ciafre, SA, Galardi, S, Mangiola, A, Ferracin, M, Liu, CG, Sabatino, G, Negrini, M, Maira, G, Croce, CM, Farace, MG (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334: pp. 1351-1358 CrossRef
9. Conti, A, Aguennouz, M, La Torre, D, Tomasello, C, Cardali, S, Angileri, FF, Maio, F, Cama, A, Germano, A, Vita, G, Tomasello, F (2009) miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV astrocytic tumors. J Neurooncol 93: pp. 325-332 CrossRef
10. Li, P, Lu, X, Wang, Y, Sun, L, Qian, C, Yan, W, Liu, N, You, Y, Fu, Z (2010) MiR-181b suppresses proliferation of and reduces chemoresistance to temozolomide in U87 glioma stem cells. J Biomed Res 24: pp. 436-443 CrossRef
11. Adiga, SK, Jagetia, GC (1999) Effect of teniposide (VM-26) on the cell survival, micronuclei-induction and lactate dehydrogenase activity on V79 cells. Toxicology 138: pp. 29-41 CrossRef
12. Stewart, DJ, Richard, MT, Hugenholtz, H, Dennery, J, Nundy, D, Prior, J, Montpetit, V, Hopkins, HS (1984) Penetration of teniposide (VM-26) into human intracerebral tumors. Preliminary observations on the effect of tumor type, rate of drug infusion and prior treatment with amphotericin B or oral glycerol. J Neurooncol 2: pp. 315-324 CrossRef
13. You, Y (2005) Podophyllotoxin derivatives: current synthetic approaches for new anticancer agents. Curr Pharm Des 11: pp. 1695-1717 CrossRef
14. Li, J, Chen, W, Zhang, P, Li, N (2006) Topoisomerase II trapping agent teniposide induces apoptosis and G2/M or S phase arrest of oral squamous cell carcinoma. World J Surg Oncol 4: pp. 41
文摘
Background Although the incidence of glioma is relatively low, it is the most malignant tumor of the central nervous system. The prognosis of high-grade glioma patient is very poor due to the difficulties in complete resection and resistance to radio-/chemotherapy. Therefore, it is worth investigating the molecular mechanisms involved in glioma drug resistance. MicroRNAs have been found to play important roles in tumor progression and drug resistance. Our previous work showed that miR-181b is involved in the regulation of temozolomide resistance. In the current study, we investigated whether miR-181b also plays a role in antagonizing the effect of teniposide. Methods MiR-181b expression was measured in 90 glioma patient tissues and its relationship to prognosis of these patients was analyzed. Cell sensitivity to teniposide was tested in 48 primary cultured glioma samples. Then miR-181b stably overexpressed U87 cells were generated. The candidate genes of miR-181b from our previous study were reanalyzed, and the interaction between miR-181b and target gene MDM2 was confirmed by dual luciferase assay. Cell sensitivity to teniposide was detected on miR-181b over expressed and MDM2 down regulated cells. Results Our data confirmed the low expression levels of miR-181b in high-grade glioma tissues, which is related to teniposide resistance in primary cultured glioma cells. Overexpression of miR-181b increased glioma cell sensitivity to teniposide. Through target gene prediction, we found that MDM2 is a candidate target of miR-181b. MDM2 knockdown mimicked the sensitization effect of miR-181b. Further study revealed that miR-181b binds to the 3-UTR region of MDM2 leading to the decrease in MDM2 levels and subsequent increase in teniposide sensitivity. Partial restoration of MDM2 attenuated the sensitivity enhancement by miR-181b. Conclusions MiR-181b is an important positive regulator on glioma cell sensitivity to teniposide. It confers glioma cell sensitivity to teniposide through binding to the 3-UTR region of MDM2 leading to its reduced expression. Our findings not only reveal the novel mechanism involved in teniposide resistance, but also shed light on the optimization of glioma treatment in the future.
| |
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.
| |
