The Research Progress of SiRNA Targeting Notch1 on Tumor Cells: A Mini Review of the State of the Art

REVIEW
Lanfen Huo¹, Shaoling Wu¹*, Zhonghai Chi², Xindong Zhao³

¹Department of Hematology, Affiliated Hospital, Qingdao University, Shandong, P.R. China; ²Hospitals of Traditional Chinese and Western Medicine, Cangzhou city, Hebei, P.R. China;  ³Department of Hematology, Medical College of Qingdao University, Qingdao, Shandong, P.R. China

*Corresponding authors: Prof. Shaoling Wu, Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, , P.R. China; E-mail:  qdwushaoling@163.com

Published: September 12, 2016.  DOI: 10.21103/Article6(3)_RA1

Abstract: 

Notch signaling is a highly conserved signaling pathway, playing an important role in a variety of cell differentiation, development and regulation. Notch signaling includes Notch1-4; Notch1 gene encodes Notch1 signaling that can shorten cell cycle, enhance cell proliferation, inhibit cell differentiation, and promote apoptosis. Mutation and overexpression of the Notch1 gene may induce tumorigenesis, which plays an important role in the development of tumors across a variety of signaling pathways. Currently, using RNA interference technology (RNAi) synthesizing small interference RNA (siRNA) targeting Notch1 gene（siNotch1）has become a hot topic, and clinical application of gene silencing has also obtained a certain therapeutic effect. In this paper, the application of Notch1 gene silencing in tumor progress was reviewed.

Keywords: 
RNAi; Notch signaling; Notch1 gene; tumor cells.
References: 
  1.  Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999; 284(5415):770-6.
  2. Cullion K, Draheim KM, Hermance N, Tammam J, Sharma VM, Ware C, et al. Targeting the Notch1 and mTOR pathways in a mouse T-ALL model. Blood. 2009; 113(24): 6172-81.
  3. Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood. 2002; 99(9): 3398-403.
  4.  Pancewicz J, Taylor JM, Datta A, Baydoun HH, Waldmann TA, Hermine O, Nicot C. Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia. Proc Natl Acad Sci USA. 2010; 107(38):16619-24.
  5.  Weng AP, Ferranndo AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-lrizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004; 306(5694): 269-71.
  6.  Wang XX, Wu SL, Zhao XD, Liu XP, Chang C. The expression and signifiance of Notch1 protein in lymphoma. Med J QiLu. 2013; 28(1):8-10.
  7.  Li GH, Huang SY, Kang ZJ, Xu H, Liang YM. Research advance of notch signal in ex vivo expansion of hematopoietic progenitor cells – review. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16(5):1227-31. [Article in Chinese].
  8. Phng LK, Potente M, Leslie JD, Babbage J, Nyqvist D, Lobov I, et al. Nrarp coordinates endothelial Notch and Wnt signaling to control vessel density in angiogenesis. Dev Cell. 2009; 16(1): 70-82.
  9. Tsukumo S, Yasutomo K. Notch governing mature T cell differentiation. J Immunol. 2004;173(12):7109-13.
  10.  Hassan WA, Yoshida R, Kudoh S, Hassegawa K, Niimori-Kita K, Ito T. Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines. Lung Cancer. 2014; 86(3): 304–10.
  11. Sun HW, Wu C, Tan HY, Wang QS. Combination DLL4 with Jagged1-siRNA can enhance inhibition of the proliferation and invasiveness activity of human gastric carcinoma by Notch1/VEGF pathway. Hepatogastroenterology. 2012; 59(115):924-9.
  12. Liu H. Effects of siRNA targeting Notch1 on the proliferation of and apoptosis in xenografted human hepatocellular carcinoma cells in nude mice. China Journal of Modern Medicine. 2012; 22(4):15-19.
  13. Du X, Wang YH, Wang ZQ, Cheng Z, Li Y, Hu JK, et al. Down-regulation of Notch1 by small interfering RNA enhances chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2014; 43(3):313-8. [Article in Chinese].
  14. Zhang Z, Wang K, Cao ZL, Hao ZQ, Guo FF. Effect of interference of Notch1 by siRNA on proliferation in renal cell carcinoma Caki-1 cells. Journal of Modern Oncology. 2014; 22(2):292-5.
  15. Ai X, Wu Z, Shi TP, Liu SL, Wang C, Zhang GX, et al. The influence of shRNA-induced Notch1 gene silencing on the biological behavior of bladder cancer cell line BIU87. Journal of Clinical Urology. 2009; 24(5):389-92.
  16. Wang Z, Zhang Y, Li Y, Banerjee S, Liao J, Sarkar FH. Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells. Mol Cancer Ther. 2006; 5(3):483-93.
  17.  Bin Hafeez B, Adhami VM, Asim M, Siddiqui IA, Bhat KM, Zhong W, et al. Targeted knockdown of Notch1 inhibits invasion of human prostate cancer cells concomitant with inhibition of matrix metalloproteinase-9 and urokinase plasminogen activator. Clin Cancer Res. 2009; 15(2):452-9.
  18.  Wang Z, Li Y, Banerjee S, Kong D, Ahmad A, Nogueira V, et al. Down-regulation of Notch-1 and Jagged-1 inhibits prostate cancer cell growth, migration and invasion, and induces apoptosis via inactivation of Akt, mTOR, and NF-κB signaling pathways. J Cell Biochem. 2010; 109(4):726–36.
  19. Sun Y, Zhang R, Zhou S, Ji Y. Overexpression of Notch1 is associated with the progression of cervical cancer. Oncol Lett. 2015; 9(6): 2750-6.
  20. Yang YP, Li W, Lin H, Du ZH, Wang GJ. Therapeutic effects of proton-sponge-coated QD-siRNA targeting Notch1 protein on leukemia. Journal of Immunology. 2013; 29(06): 474-79. [Article in Chinese].
  21. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev. 2006; 20(15):2096-109.
  22. Kamstrup MR, Gjerdrum LM, Biskup E, Lauenborg BT, Ralfkiaer E, Woetmann A, et al. Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma. Blood. 2010; 116(14): 2504-12.
  23. Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, et al. Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res. 2005; 65(6): 2353-63.
  24. Xu P, Qiu M, Zhang Z, Kang R, Jiang R, Jia Z, et al. The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo. J Neurooncol. 2010; 97(1):41-51.
  25.  Mao J, Mou QJ, Li LH, Tao YJ, Fan ZJ, Wang B, et al. Effect on proliferation and apoptosis of human breast cancer line MCF-7 with Notch1 gene silencing by RNA interference. J Clin Exp Pathol. 2012; 28(01):11-4.
  26. Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005; 65(18): 8530-7.
  27. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010; 464(7291):1067-70.
  28. Schultheis B, Strumberg D, Santel A, Vank C, Gebhardt F, Keil O, et al. First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J Clin Oncol. 2014; 32(36):4141-8.

The fully formatted PDF version is available.

Download Article

Int J Biomed. 2016;6(3):163-166. © 2016 International Medical Research and Development Corporation. All rights reserved.