Drug name: shRNA

Related CSCTT Targets

KIT (SCFR) [ref.1]P10721
HOTAIR [ref.2]
SMO [ref.3]Q99835
EZH2 [ref.4]Q15910
Aurora A [ref.5]O14965
Telomerase [ref.6]O14746
ROCK1 [ref.7]P70335
PKCδ [ref.8]Q05655
STAT3 [ref.6,9]P40763
GD3S [ref.10]Q92185
Notch1 [ref.11,12]P46531
Notch4 [ref.11]Q99466
Pyk2 [ref.13]Q14289
L1CAM [ref.14]P32004
c-Myc [ref.15]P01106
BMI1 [ref.16]P35226
ZEB1 [ref.17]P37275
ZEB2 [ref.17]O60315
Chk1 [ref.18]O14757
RAF1 [ref.19]P04049
CTGF [ref.20]P29279
uPAR [ref.21]Q03405
Ubiquitin Ligases [ref.22]
VDAC2 [ref.23]P45880
LRP8 [ref.24]Q14114


A small hairpin RNA or short hairpin RNA (shRNA) is a sequence of RNA that makes a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. The promoter choice is essential to achieve robust shRNA expression. At first, polymerase III promoters such as U6 and H1 were used; however, these promoters lack spatial and temporal control. As such, there has been a shift to using polymerase II promoters to regulate expression of shRNA. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover.

Expression of shRNA in cells can be obtained by delivery of plasmids or through viral or bacterial vectors. Through transfection vectors to cells to obtain shRNA expression can be accomplished using commercially available reagents in vitro, but not in vivo and limited the utility.

Several challenges typically confront shRNA-based therapeutics. The most significant challenge is delivery. shRNA is typically delivered through use of a vector, and although they are generally efficient, they pose significant safety concerns. In particular, viral based gene therapy approaches have proved dangerous in past clinical trials. Potential oversaturation of RISC is also a problem. If the shRNA is expressed at levels that are too high the cell might not be able to correctly process the endogenous RNA which could cause significant problems. Another challenge is the possibility that the patient might mount an immune response against the therapy. Finally, there might be off-target effects and the shRNA could silence other unintended genes. In developing successful new shRNA-based therapeutics, all of these challenges must be taken into account.




  • [1] Silencing stem cell factor attenuates stemness and inhibits migration of cancer stem cells derived from Lewis lung carcinoma cells.
    Wang, L., et al. (2015). Tumour Biol. [ 26666817 ]
  • [2] Decreasing lncRNA HOTAIR expression inhibits human colorectal cancer stem cells.
    Dou, J., et al. (2016). Am J Transl Res 8(1): 98-108. [ 27069543 ]
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    Clement, V., et al. (2007).Curr Biol 17(2): 165-172. [ 17196391 ]
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    Chang, C. J., et al. (2011). Cancer Cell 19(1): 86-100. [ 21215703 ]
  • [5] Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells.
    Cammareri, P., et al. (2010). Cancer Res 70(11): 4655-4665. [ 20460511 ]
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    Chung, S. S., et al. (2013). PLoS One 8(12): e83971. [ 24386318 ]
  • [7] ROCK1 inhibition promotes the self-renewal of a novel mouse mammary cancer stem cell.
    Castro, D. J., et al. (2013). Stem Cells 31(1): 12-22. [ 22961723 ]
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    Chen, Z., et al. (2014). BMC Cancer 14: 90. [ 24528676 ]
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    Chung, S. S., et al. (2014). Int J Oncol 44(2): 403-411. [ 24297508 ]
  • [10] GD3 synthase regulates epithelial–mesenchymal transition and metastasis in breast cancer
    Sarkar T R, Battula V L, Werden S J, et al. Oncogene, 2014. [ 25109336 ]
  • [11] Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.
    Harrison, H., et al. (2010). Cancer Res 70(2): 709-718. [ 20068161 ]
  • [12] NOTCH1 signaling promotes chemoresistance via regulating ABCC1 expression in prostate cancer stem cells.
    Liu, C., et al. (2014). Mol Cell Biochem 393(1-2): 265-270. [ 24782036 ]
  • [13] Compensatory function of Pyk2 protein in the promotion of focal adhesion kinase (FAK)-null mammary cancer stem cell tumorigenicity and metastatic activity.
    Fan, H. and J. L. Guan (2011). J Biol Chem 286(21): 18573-18582. [ 21471206 ]
  • [14] Targeting cancer stem cells through L1CAM suppresses glioma growth.
    Bao, S., et al. (2008). Cancer Res 68(15): 6043-6048. [ 18676824 ]
  • [15] c-Myc is required for maintenance of glioma cancer stem cells.
    Wang, J., et al. (2008). PLoS One 3(11): e3769. [ 19020659 ]
  • [16] The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma.
    Chiba, T., et al. (2008). Cancer Res 68(19): 7742-7749. [ 18829528 ]
  • [17] The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs.
    Wellner, U., et al. (2009). Nat Cell Biol 11(12): 1487-1495. [ 19935649 ]
  • [18] Chk1 knockdown confers radiosensitization in prostate cancer stem cells.
    Wang, X., et al. (2012). Oncol Rep 28(6): 2247-2254. [ 23027394 ]
  • [19] EZH2 promotes expansion of breast tumor initiating cells through activation of RAF1-beta-catenin signaling.
    Chang, C. J., et al. (2011). Cancer Cell 19(1): 86-100. [ 21215703 ]
  • [20] MicroRNA-145 is downregulated in glial tumors and regulates glioma cell migration by targeting connective tissue growth factor.
    Lee, H. K., et al. (2013). PLoS One 8(2): e54652. [ 23390502 ]
  • [21] Urokinase-type plasminogen activator receptor (uPAR)-mediated regulation of WNT/beta-catenin signaling is enhanced in irradiated medulloblastoma cells.
    Asuthkar, S., et al. (2012). J Biol Chem 287(24): 20576-20589. [ 22511755 ]
  • [22] Knockdown of ubiquitin ligases in glioblastoma cancer stem cells leads to cell death and differentiation.
    Low, J., et al. (2012). J Biomol Screen 17(2): 152-162. [ 21956171 ]
  • [23] VDAC2 interacts with PFKP to regulate glucose metabolism and phenotypic reprogramming of glioma stem cells.
    Cell Death Dis.2018 Sep 24;9(10):988.. [ 30250190 ]
  • [24] Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer.
    Cancer Lett.2018 Dec 1;438:165-173.. [ 30227220 ]

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