MicroRNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway

详细信息    查看全文

• 作者：Te Liu (1) (3)
  Wenxing Qin (2)
  Lengchen Hou (1)
  Yongyi Huang (4)
  
  1. Shanghai Tenth People鈥檚 Hospital ; Medical School ; Tongji University ; Shanghai ; 200072 ; China
  3. Shanghai Geriatric Institute of Chinese Medicine ; Longhua Hospital ; Shanghai University of Traditional Chinese Medicine ; Shanghai ; 200031 ; China
  2. Department of Medical Oncology ; Shanghai Changzheng Hospital ; The Second Military Medical University ; Shanghai ; 200070 ; China
  4. Laboratoire PROTEE ; B芒timent R ; Universit茅 du Sud Toulon-Var ; 83957 ; La Garde Cedex ; France
  
• 关键词：Ovarian cancer ; Cancer stem cells ; LKB1 ; p53 ; p21/WAF1 pathway ; MicroRNA ; 17 ; Proliferation ; Tumorigenicity
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：36
• 期：3
• 页码：1881-1893
• 全文大小：8,347 KB
• 参考文献：1. Liu, T, Cheng, W, Lai, D, Huang, Y, Guo, L (2010) Characterization of primary ovarian cancer cells in different culture systems. Oncol Rep 23: pp. 1277-84 CrossRef
  2. Qin, W, Ren, Q, Liu, T, Huang, Y, Wang, J (2013) MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1. Febs Lett 587: pp. 1434-9 CrossRef
  3. Cheng, W, Liu, T, Wan, X, Gao, Y, Wang, H (2012) MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J 279: pp. 2047-59 CrossRef
  4. Ollila, S, Makela, TP (2011) The tumor suppressor kinase LKB1: lessons from mouse models. J Mol Cell Biol 3: pp. 330-40 CrossRef
  5. Krock, B, Skuli, N, Simon, MC (2011) The tumor suppressor LKB1 emerges as a critical factor in hematopoietic stem cell biology. Cell Metab 13: pp. 8-10 CrossRef
  6. Veeranki, S, Hwang, SH, Sun, T, Kim, B, Kim, L (2011) LKB1 regulates development and the stress response in Dictyostelium. Dev Biol 360: pp. 351-7 CrossRef
  7. Zeng, PY, Berger, SL (2006) LKB1 is recruited to the p21/WAF1 promoter by p53 to mediate transcriptional activation. Cancer Res 66: pp. 10701-8 CrossRef
  8. Liang, X, Wang, P, Gao, Q, Xiang, T, Tao, X (2010) Endogenous LKB1 knockdown accelerates G(1)/S transition through p53 and p16 pathways. Cancer Biol Ther 9: pp. 156-60 CrossRef
  9. Lutzner, N, Kalbacher, H, Krones-Herzig, A, Rosl, F (2012) FOXO3 is a glucocorticoid receptor target and regulates LKB1 and its own expression based on cellular AMP levels via a positive autoregulatory loop. PLoS One 7: pp. e42166 CrossRef
  10. Lutzner, N, De-Castro, AJ, Rosl, F (2012) Gene expression of the tumour suppressor LKB1 is mediated by Sp1, NF-Y and FOXO transcription factors. PLoS One 7: pp. e32590 CrossRef
  11. Denison, FC, Smith, LB, Muckett, PJ, O鈥橦ara, L, Carling, D, Woods, A (2011) LKB1 is an essential regulator of spermatozoa release during spermiation in the mammalian testis. PLoS One 6: pp. e28306 CrossRef
  12. Cao, Y, Li, H, Liu, H, Zhang, M, Hua, Z, Ji, H (2011) LKB1 regulates TCR-mediated PLCgamma1 activation and thymocyte positive selection. Embo J 30: pp. 2083-93 CrossRef
  13. Wei, C, Bhattaram, VK, Igwe, JC, Fleming, E, Tirnauer, JS (2012) The LKB1 tumor suppressor controls spindle orientation and localization of activated AMPK in mitotic epithelial cells. PLoS One 7: pp. e41118 CrossRef
  14. Gan, B, Hu, J, Jiang, S, Liu, Y, Sahin, E, Zhuang, L (2010) Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468: pp. 701-4 CrossRef
  15. Nakada, D, Saunders, TL, Morrison, SJ (2010) Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 468: pp. 653-8 CrossRef
  16. Gurumurthy, S, Xie, SZ, Alagesan, B, Kim, J, Yusuf, RZ, Saez, B (2010) The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 468: pp. 659-63 CrossRef
  17. Udd, L, Makela, TP (2011) LKB1 signaling in advancing cell differentiation. Fam Cancer 10: pp. 425-35 CrossRef
  18. Vaahtomeri, K, Makela, TP (2011) Molecular mechanisms of tumor suppression by LKB1. Febs Lett 585: pp. 944-51 CrossRef
  19. Liu, W, Monahan, KB, Pfefferle, AD, Shimamura, T, Sorrentino, J, Chan, KT (2012) LKB1/STK11 inactivation leads to expansion of a prometastatic tumor subpopulation in melanoma. Cancer Cell 21: pp. 751-64 CrossRef
  20. Brown, KA, McInnes, KJ, Takagi, K, Ono, K, Hunger, NI, Wang, L (2011) LKB1 expression is inhibited by estradiol-17beta in MCF-7 cells. J Steroid Biochem Mol Biol 127: pp. 439-43 CrossRef
  21. Lee, CG, Kim, YW, Kim, EH, Meng, Z, Huang, W, Hwang, SJ (2012) Farnesoid X receptor protects hepatocytes from injury by repressing miR-199a-3p, which increases levels of LKB1. Gastroenterology 142: pp. 1206-17 CrossRef
  22. Chen, H, Untiveros, GM, McKee, LA, Perez, J, Li, J, Antin, PB (2012) Micro-RNA-195 and -451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One 7: pp. e41574 CrossRef
  23. Fang, L, Li, H, Wang, L, Hu, J, Jin, T, Wang, J (2014) MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget 5: pp. 2974-87
  24. Wu, SY, Lin, KC, Chiou, JF, Jeng, SC, Cheng, WH, Chang, CI (2013) MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells. Strahlenther Onkol 189: pp. 675-83 CrossRef
  25. Shen, Y, Lu, L, Xu, J, Meng, W, Qing, Y, Liu, Y (2013) Bortezomib induces apoptosis of endometrial cancer cells through microRNA-17-5p by targeting p21. Cell Biol Int 37: pp. 1114-21 CrossRef
  26. Yu, Z, Willmarth, NE, Zhou, J, Katiyar, S, Wang, M, Liu, Y (2010) MicroRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling. Proc Natl Acad Sci U S A 107: pp. 8231-6 CrossRef
  27. Kim, K, Chadalapaka, G, Lee, SO, Yamada, D, Sastre-Garau, X, Defossez, PA (2012) Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene 31: pp. 1034-44 CrossRef
  28. Liu, T, Chen, Q, Huang, Y, Huang, Q, Jiang, L, Guo, L (2012) Low microRNA-199a expression in human amniotic epithelial cell feeder layers maintains human-induced pluripotent stem cell pluripotency via increased leukemia inhibitory factor expression. Acta Biochim Biophys Sin (Shanghai) 44: pp. 197-206 CrossRef
  29. Shen, DZ, Xin, SL, Chen, C, Liu, T (2013) Effect of atorvastatin on expression of TLR4 and NF-kappaB p65 in atherosclerotic rabbits. Asian Pac J Trop Med 6: pp. 493-6 CrossRef
  30. Zhang, S, Balch, C, Chan, MW, Lai, HC, Matei, D, Schilder, JM (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68: pp. 4311-20 CrossRef
  31. Andersson, E, Villabona, L, Bergfeldt, K, Carlson, JW, Ferrone, S, Kiessling, R (2012) Correlation of HLA-A02* genotype and HLA class I antigen down-regulation with the prognosis of epithelial ovarian cancer. Cancer Immunol Immunother 61: pp. 1243-53 CrossRef
  32. Rubatt, JM, Darcy, KM, Tian, C, Muggia, F, Dhir, R, Armstrong, DK (2012) Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study. Gynecol Oncol 125: pp. 421-6 CrossRef
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

The mechanism underlying the development of human ovarian cancer is poorly understood. The liver kinase protein, LKB1, is hypothesized to play a pivotal role in tumor cell proliferation and invasion capacity through regulation of p53 and p21/WAF1 expression. Previous studies suggest LKB1 may, in turn, be regulated by microRNA-17. Here, we examined the role of miR-17 in the expression of LKB1 and the downstream effects on proliferation and invasion capacity of normal ovarian cancer cells (OCCs) and ovarian stem cells. In this study, both the mRNA and protein expression levels of LKB1, p53, and p21 decreased in OCCs following transfection with a miR-17 expression plasmid. MiR-17 expression affected cell cycle regulation and stimulated the proliferation and invasion capacity of OCCs in vitro. ChIP assays indicated that the binding efficiency of p53 to the p21/WAF1 gene promoter was much lower in miR-17 transfected OCCs than in OCCs transfected with a mutated miR-17. Co-immunoprecipitation and western blotting showed significantly lower levels of p53 and p53 Ser15-pho in the miR-17 transfected OCCs as compared to the mutant miR-17 transfected OCCs. Xenograft experiments confirmed that suppression of tumor growth in vivo occurred in the absence of functional miR-17. These findings suggest that mature miR-17 expression may have an important role in the pathogenesis of human ovarian tumors through its interference with the LKB1-p53-p21/WAF1 pathway expression by epigenetic modification. These findings are of potential importance in the identification of novel therapeutic targets in human ovarian cancer.