2015年3月3日訊 /生物谷BIOON/ --近日,國際生物學期刊Cell Research在線刊登了美國南加州大學研究人員的一項最新研究成果,他們應用植物miRNA能夠被哺乳動物消化道細胞消化吸收,進入組織發揮基因調控這一發現,開發了一種口服miRNA混合劑給藥系統,並通過動物實驗證明口服腫瘤抑制性miRNA能夠有效抑制腫瘤生長。
miRNA是一類小的非編碼RNA,幾乎存在於所有真核生物中,並在調控基因表達方面發揮重要作用。在人類所有蛋白質編碼基因中,約有60%的基因會受到miRNA調控,機體幾乎每一個生理過程都會受到miRNA的影響。同時也有許多疾病與miRNA失調相關。之前研究發現在腫瘤細胞中,一類特定的作為腫瘤抑制因子的miRNA其表達受到下調,恢復這類miRNA表達能夠抑制動物模型腫瘤發生。因此如何上調這類miRNA使其發揮腫瘤抑制因子作用越來越得到人們的廣泛關注。
研究人員發現來自於食物的植物miRNAs能夠被哺乳動物消化道細胞吸收,並被包裝成微泡轉運進入血液,並被輸送到各個組織,調控基因表達。因此研究人員藉助於這一發現開發了一種有效的給藥系統,他們將多種腫瘤抑制因子miRNAs的混合劑以口服形式處理結腸癌小鼠模型,結果發現小鼠腫瘤負荷減少,並且在實驗期間均保持健康和正常的體重增加,沒有明顯毒性。結果表明用腫瘤抑制性miRNA模擬植物小RNA即可通過口服的形式給與結腸癌小鼠模型並發揮腫瘤抑制功能,減小腫瘤負荷。
這項研究成果表明,應用改造的可食用植物產生具有腫瘤抑制效應的miRNA,並以此作為有效,無毒,廉價的化療策略將會具有非常重大的應用前景。(生物谷Bioon.com)
A novel chemopreventive strategy based on therapeutic microRNAs produced in plants
Sizolwenkosi Mlotshwa1,*, Gail J Pruss1,*, John L MacArthur1, Matthew W Endres1, Celestia Davis1, Lorne J Hofseth2, Maria Marjorette Pe?a1 and Vicki Vance1
MicroRNAs (miRNAs) are small non-coding RNAs that play a critical role in regulation of gene expression in nearly all eukaryotic organisms, including mammals. In humans, an estimated 60% of all protein-coding genes are targeted by miRNAs, affecting virtually every physiological process in the body1. In addition, a diverse array of human diseases is associated with dysregulation of miRNAs2. In many forms of cancer, for example, certain miRNAs, termed tumor suppressor miRNAs, are downregulated in diseased cells. Restoration of the downregulated tumor suppressor miRNA has been shown to block one or more steps in oncogenesis in animal models and cell culture systems. Thus, the therapeutic potential of tumor suppressor miRNAs has been experimentally confirmed and is now widely recognized. However, systemic delivery of such therapeutic small RNAs in humans is challenging and numerous delivery options are currently under investigation.