Rapid functional screening of effective siRNAs against Plk1 and its growth inhibitory effects in laryngeal carcinoma ce
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Plk 1 is overexpressed in many human malignancies including laryngeal carcinoma. However, its therapeutic potential has been never examined in laryngeal carcinoma. In the present study, a simple cellular morphology-based strategy was firstly proposed for rapidly screening the effective siRNAs against Plk1. Furthermore, we investigated the effects of Plk1 depletion via a novel identified effective siRNA against Plk1, Plk1siRNA-607, on human laryngeal carcinoma Hep-2 cells. The results indicated that Plk1 siRNA-607 transfection resulted in a significant inhibition in Plk1 expression in cells, and subsequently caused a dramatic mitotic cell cycle arrest followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of the laryngeal carcinoma cells. Taken together, our present study not only suggests a simple strategy for rapidly screening effective siRNAs against Plk1 but also implicates that Plk1 may serve as a potential therapeutic target in human laryngeal carcinoma.
Abstract
Plk 1 is overexpressed in many human malignancies including laryngeal carcinoma. However, its therapeutic potential has been never examined in laryngeal carcinoma. In the present study, a simple cellular morphology-based strategy was firstly proposed for rapidly screening the effective siRNAs against Plk1. Furthermore, we investigated the effects of Plk1 depletion via a novel identified effective siRNA against Plk1, Plk1siRNA-607, on human laryngeal carcinoma Hep-2 cells. The results indicated that Plk1 siRNA-607 transfection resulted in a significant inhibition in Plk1 expression in cells, and subsequently caused a dramatic mitotic cell cycle arrest followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth and viability of the laryngeal carcinoma cells. Taken together, our present study not only suggests a simple strategy for rapidly screening effective siRNAs against Plk1 but also implicates that Plk1 may serve as a potential therapeutic target in human laryngeal carcinoma.
참고문헌 (26)
- Glover, D. M., "Polo-like kinases: a team that plays throughout mitosis", Genes. Dev., 12, pp.3777~3787 (1998)
- Golsteyn, R. M., "Cell cycle analysis and chromosomal localization of human Plk1, a putative homologue of the mitotic kinases Drosophila polo and Saccharomyces cerevisiae Cdc5", J. Cell Sci., 107, pp.1509~1517 (1994)
- Strebhardt, K., "Targeting polo-like kinase 1 for cancer therapy", Nat. Rev. Cancer, 6, pp.321~330 (2006)
- Chopra, P., "Polo-like kinase inhibitors: an emerging opportunity for cancer therapeutics", Expert. Opin. Investig. Drugs, 19, pp.27~43 (2010)
- Degenhardt, Y., "Targeting Pololike kinase in cancer therapy", Clin. Cancer Res., 16, pp.384~389 (2010)
- Takai, N., "Polo-like kinases (Plks) and cancer", Oncogene., 24, pp.287~291 (2005)
- Knecht, R., "Prognostic significance of polo-like kinase (PLK) expression in squamous cell carcinomas of the head and neck", Cancer Res., 59, pp.2794~2797 (1999)
- Spänkuch-Schmitt, B., "Effect of RNA silencing of polo-like kinase-1 (PLK1) on apoptosis and spindle formation in human cancer cells", J. Natl. Cancer Inst., 94, pp.1863~1877 (2002)
- Rizki, A., "Polo-like kinase 1 is involved in invasion through extracellular matrix", Cancer Res., 67, pp.11106~11110 (2007)
- Liu, X., "Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells", Proc. Natl. Acad. Sci. U.S.A., 통권 : 100, pp.5789~5794 (2003)
- Reagan-Shaw, S., "Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer", FASEB J., 19, pp.611~613 (2005)
- Liu, X., "Normal cells, but not cancer cells, survive severe Plk1 depletion", Mol. Cell Biol., 26, pp.2093~2108 (2006)
- Bumcrot, D., "RNAi therapeutics: a potential new class of pharmaceutical drugs", Nat. Chem. Biol., 2, pp.711~719 (2006)
- Tiemann, K., "RNAi-based therapeutics-current status, challenges and prospects", EMBO Mol. Med., 1, pp.142~151 (2009)
- Bu, Y., "Silencing of polo-like kinase (Plk) 1 via siRNA causes inhibition of growth and induction of apoptosis in human esophageal cancer cells", Oncology, 74, pp.198~206 (2008)
- Marioni, G., "Current opinion in diagnosis and treatment of laryngeal carcinoma", Cancer Treat. Rev., 32, pp.504~515 (2006)
- Papadas, T. A., "Survival after laryngectomy: a review of 133 patients with laryngeal carcinoma", Eur. Arch. Otorhinolaryngol., 267, pp.1095~1101 (2010)
- Juan, G., "Histone H3 phosphorylation and expression of cyclins A and B1 measured in individual cells during their progression through G2 and mitosis", Cytometry, 32, pp.71~77 (1998)
- Tilesi, F., "Design and validation of siRNAs and shRNAs", Curr. Opin. Mol. Ther., 11, pp.156~164 (2009)
- Huesken, D., "Design of a genome-wide siRNA library using an artificial neural network", Nat. Biotechnol., 23, pp.995~1001 (2005)
- Hung, C. F., "A novel siRNA validation system for functional screening and identification of effective RNAi probes in mammalian cells", Biochem. Biophys. Res. Commun., 346, pp.707~720 (2006)
- Luo, Q., "Selection and validation of optimal siRNA target sites for RNAi-mediated gene silencing", Gene, 395, pp.160~169 (2007)
- Liu, X., "Activation of Cdc2", cyclin B and inhibition of centrosome amplification in cells depleted of Plk1 by siRNA, 2002, pp.통권 : 99, 8672~8676
- Roshak, A. K., "The human polo-like kinase, PLK, regulates cdc2", cyclin B through phosphorylation and activation of the cdc25C phosphatase, 2000, pp.12, 405~411
- Yamada, S., "Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas", Oncogene, 23, pp.5901~5911 (2004)
- Livak, K. J., "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method", Methods, 25, pp.402~408 (2001)
