Drug name: siRNA

Related CSCTT Targets

Oct4 [ref.1]Q01860
SMO [ref.2]Q99835
EZH2 [ref.3]Q15910
PKCδ [ref.4]Q05655
DCLK1 [ref.5]O15075
Notch1 [ref.6,7,8]P46531
Notch4 [ref.7]Q99466
Notch3 [ref.9]Q9UM47
Mcl-1 [ref.10]Q07820
β-Catenin [ref.11]P35222
Snail [ref.12]O95863
LGR5 [ref.13]O75473
ARTN [ref.14]Q5T4W7
TB-4 [ref.15]P62328
ZEB1 [ref.16,20]P37275
ZEB2 [ref.16]O60315
PKCε [ref.17]Q02156
Nanog [ref.17]Q9H9S0
microRNA 21 [ref.18]
FOXM1 [ref.19]Q08050
VDAC1 [ref.21]P21796
TOPK [ref.22]Q96KB5
S100B [ref.23]P04271
LRP8 [ref.24]Q14114


Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length. siRNA plays many roles, but it is most notable in the RNA interference (RNAi) pathway, where it interferes with the expression of specific genes with complementary nucleotide sequences. siRNA functions by causing mRNA to be broken down after transcription, resulting in no translation. siRNA also acts in RNAi-related pathways, e.g., as an antiviral mechanism or in shaping the chromatin structure of a genome. The complexity of these pathways is only now being elucidated.

siRNAs have a well-defined structure: a short (usually 20 to 24-bp) double-stranded RNA (dsRNA) with phosphorylated 5' ends and hydroxylated 3' ends with two overhanging nucleotides. The Dicer enzyme catalyzes production of siRNAs from long dsRNAs and small hairpin RNAs. siRNAs can also be introduced into cells by transfection. Since in principle any gene can be knocked down by a synthetic siRNA with a complementary sequence, siRNAs are an important tool for validating gene function and drug targeting in the post-genomic era.

Given the ability to knock down, in essence, any gene of interest, RNAi via siRNAs has generated a great deal of interest in both basic and applied biology. There are an increasing number of large-scale RNAi screens that are designed to identify the important genes in various biological pathways. Because disease processes also depend on the activity of multiple genes, it is expected that in some situations turning off the activity of a gene with an siRNA could produce a therapeutic benefit.

Phase I results of the first two therapeutic RNAi trials (indicated for age-related macular degeneration, aka AMD) reported at the end of 2005 that siRNAs are well tolerated and have suitable pharmacokinetic properties.

Small interfering RNASchema



  • [1] Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis.
    Hu, T., et al. (2008). Cancer Res 68(16): 6533-6540. [ 18701476 ]
  • [2] Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs.
    Ahmad, A., et al. (2013). J Hematol Oncol 6(1): 77. [ 24199791 ]
  • [3] Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression.
    Bao, B., et al. (2012). Cancer Res 72(1): 335-345. [ 22108826 ]
  • [4] Protein kinase Cdelta is a therapeutic target in malignant melanoma with NRAS mutation.
    Takashima, A., et al. (2014). ACS Chem Biol 9(4): 1003-1014. [ 24506253 ]
  • [5] Hepatitis C virus-induced cancer stem cell-like signatures in cell culture and murine tumor xenografts.
    Ali, N., et al. (2011). J Virol 85(23): 12292-12303. [ 21937640 ]
  • [6] Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab.
    Magnifico, A., et al. (2009). Clin Cancer Res 15(6): 2010-2021. [ 19276287 ]
  • [7] 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 ]
  • [8] Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells.
    Wang, Z., et al. (2011). J Cell Biochem 112(1): 78-88. [ 20658545 ]
  • [9] The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction.
    Xiao, Y., et al. (2011). Oncogene 30(3): 287-300. [ 20838375 ]
  • [10] Suppression of myeloid cell leukemia-1 (Mcl-1) enhances chemotherapy-associated apoptosis in gastric cancer cells.
    Akagi, H., et al. (2013).Gastric Cancer 16(1): 100-110. [ 22527182 ]
  • [11] beta-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.
    Condello, S., et al. (2014). Oncogene. [ 24954508 ]
  • [12] Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer.
    Chen, Y. C., et al. (2009). Biochem Biophys Res Commun 385(3): 307-313. [ 19450560 ]
  • [13] LGR5 promotes survival in human colorectal adenoma cells and is upregulated by PGE2: implications for targeting adenoma stem cells with NSAIDs.
    Al-Kharusi, M. R., et al. (2013). Carcinogenesis 34(5): 1150-1157. [ 23349017 ]
  • [14] Artemin stimulates radio- and chemo-resistance by promoting TWIST1-BCL-2-dependent cancer stem cell-like behavior in mammary carcinoma cells.
    Banerjee, A., et al. (2012). J Biol Chem 287(51): 42502-42515. [ 23095743 ]
  • [15] Quantitative mass spectrometry identifies drug targets in cancer stem cell-containing side population.
    Steiniger, S. C., et al. (2008). Stem Cells 26(12): 3037-3046. [ 18802034 ]
  • [16] Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer.
    Chu, P. Y., et al. (2013). Oral Oncol 49(1): 34-41. [ 22892238 ]
  • [17] Hyaluronan-CD44 interaction with protein kinase C(epsilon) promotes oncogenic signaling by the stem cell marker Nanog and the Production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells.
    Bourguignon, L. Y., et al. (2009). J Biol Chem 284(39): 26533-26546. [ 19633292 ]
  • [18] Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.
    Bao, B., et al. (2012). PLoS One 7(12): e50165. [ 23272057 ]
  • [19] The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells.
    Bergamaschi, A., et al. (2014). Breast Cancer Res 16(5): 436. [ 25213081 ]
  • [20] MicroRNA-200C and -150 Play an Important Role in Endothelial Cell Differentiation and Vasculogenesis by Targeting Transcription Repressor ZEB1.
    Stem Cells, 31 (9), 1749-62.. [ 23765923 ]
  • [21] VDAC1 is a molecular target in glioblastoma, with its depletion leading to reprogrammed metabolism and reversed oncogenic properties.
    Neuro Oncol.2017 Jul 1;19(7):951-964.. [ 28339833 ]
  • [22] TOPK (T-LAK cell-originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer.
    Cancer Sci.2017 Mar;108(3):488-496. [ 28075524 ]
  • [23] S100B Mediates Stemness of Ovarian Cancer Stem-Like Cells Through Inhibiting p53.
    Stem Cells.2017 Feb;35(2):325-336. [ 27501952 ]
  • [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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