Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.
Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.
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DOI：
10.1371/journal.pone.0114121
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tamura M
中科院分区：
文献类型：
--
作者：
Iizuka S;Oridate N;Nashimoto M;Fukuda S;Tamura M
头颈部鳞状细胞癌(HNSCC)表现为细胞周期蛋白D1(CCND1)表达增加。以往的研究表明，HNSCC的预后不良与细胞周期蛋白D1的过度表达有关。TRNase ZL-利用有效的基因沉默(真基因沉默)是一种具有治疗潜力的RNA介导的基因表达调控技术。这项技术是基于哺乳动物tRNase ZL独特的酶特性，即它可以通过识别目标RNA和人工小引导RNA(SgRNA)之间形成的前tRNA样复合体，在任何期望的位置切割任何目标RNA。在本研究中，我们设计了几个针对人细胞周期蛋白D1mRNA的sgRNA，以检测对HNSCC细胞的生长抑制。某些sgRNAs可降低HSC-2和HSC-3细胞中细胞周期蛋白D1mRNA和蛋白的表达水平，并抑制其增殖。这些sgRNAs和顺铂的结合显示出对癌细胞生长的相加抑制作用。这些结果表明，细胞周期蛋白D1的真正基因沉默导致抑制HNSCC细胞的生长，提示这些sgRNAs单独或与顺铂联合治疗HNSCC可能是一种有用的新疗法。
Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial small guide RNA (sgRNA). In this study, we designed several sgRNAs targeting human cyclin D1 mRNA to examine growth inhibition of HNSCC cells. Transfection of certain sgRNAs decreased levels of cyclin D1 mRNA and protein in HSC-2 and HSC-3 cells, and also inhibited their proliferation. The combination of these sgRNAs and cisplatin showed more than additive inhibition of cancer cell growth. These findings demonstrate that TRUE gene silencing of cyclin D1 leads to inhibition of the growth of HNSCC cells and suggest that these sgRNAs alone or combined with cisplatin may be a useful new therapy for HNSCCs.
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影响因子：
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