來(lái)自德國(guó)馬克斯－普朗克生物化學(xué)研究所（Max-Planck-Institute of Biochemistry）分子腫瘤學(xué)的研究人員Heiko Hermeking在本期（2007年11月）Cell子刊Cancer Cell上發(fā)表了一篇有關(guān)p53與microRNA之間
關(guān)系的綜述,，受到了本領(lǐng)域及相關(guān)研究領(lǐng)域的關(guān)注,。
微小RNA (microRNA,，簡(jiǎn)稱(chēng)miRNA)是生物體內(nèi)源長(zhǎng)度約為20－23個(gè)核苷酸的非編碼小RNA,，通過(guò)與靶mRNA的互補(bǔ)配對(duì)而在轉(zhuǎn)錄后水平上對(duì)基因的表達(dá)進(jìn)行負(fù)調(diào)控,，導(dǎo)致mRNA的降解或翻譯抑制,。對(duì)于miRNAs的研究起始于時(shí)序調(diào)控小RNA（stRNAs）,，由于miRNAs在物種進(jìn)化中相當(dāng)保守,，在植物,、動(dòng)物和真菌中發(fā)現(xiàn)的miRNAs只在特定的組織和發(fā)育階段表達(dá),，而且這種特異性和時(shí)序性，決定了組織和細(xì)胞的功能特異性,，表明miRNA在細(xì)胞生長(zhǎng)和發(fā)育過(guò)程的調(diào)節(jié)過(guò)程中起多種作用,，因此miRNA的研究受到了生物學(xué)家的廣泛關(guān)注,。
近年來(lái)，越來(lái)越多的研究證實(shí)這種小分子RNA——microRNA與高等動(dòng)植物大量基因的調(diào)節(jié)有關(guān),，并且還與癌癥等人類(lèi)疾病有關(guān),。這種分子的研究也是近年來(lái)癌癥科學(xué)領(lǐng)域一個(gè)越來(lái)越熱的研究聚焦點(diǎn)。
去年一項(xiàng)由冷泉港實(shí)驗(yàn)室完成的研究中,，發(fā)現(xiàn)了一個(gè)輔助p53途徑抑制腫瘤生長(zhǎng)的miRNA家族,，他們不僅發(fā)現(xiàn)p53能夠抑制腫瘤生長(zhǎng)甚至根除腫瘤，而且發(fā)現(xiàn)了一些增強(qiáng)p53途徑的怪物質(zhì),。在那篇文章中,，作者認(rèn)為即便在癌癥的最后階段，之前被破壞的p53途徑的再生都能使腫瘤停止生長(zhǎng),，甚至通過(guò)激活周?chē)?a href="http://hnhlg.com/news/list-54.html" target="_blank">健康細(xì)胞的免疫反應(yīng)消除腫瘤,。大多數(shù)人猜測(cè)是蛋白賦予了p53這種能力，但最新研究成果顯示是miRNA提高了p53抗腫瘤增生的效果,。
而近期,，7個(gè)研究團(tuán)體發(fā)現(xiàn)了由腫瘤抑制因子p53編碼的轉(zhuǎn)錄因子調(diào)控的miRNAs，這些研究強(qiáng)調(diào)出miRNAs：miR-34a和miR-34b/c是直接的,，保守的p53的靶標(biāo)基因,，介導(dǎo)了細(xì)胞凋亡的誘發(fā)，細(xì)胞周期的停滯以及衰老,。由于這些miRNA也許調(diào)控了數(shù)以百計(jì)的不同蛋白的表達(dá)水平,，因此這些發(fā)現(xiàn)提出了p53網(wǎng)絡(luò)一個(gè)新的，挑戰(zhàn)性的復(fù)雜平臺(tái),，綜述中也提到有關(guān)miR-34基因是p53功能的核心介導(dǎo)因子的證據(jù),。
原始出處:
Cancer Cell, Vol 12, 414-418, 13 November 2007
Minireview
p53 Enters the MicroRNA World
Heiko Hermeking1,
1 Molecular Oncology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany
Corresponding author
Heiko Hermeking
[email protected]
Recently, microRNAs, which are regulated by the transcription factor encoded by the tumor suppressor gene p53, were identified independently by seven groups. Their studies highlight the microRNAs miR-34a and miR-34b/c as direct, conserved p53 target genes that presumably mediate induction of apoptosis, cell cycle arrest, and senescence by p53. Since these microRNAs may regulate the levels of hundreds of different proteins, these findings add a new, challenging layer of complexity to the p53 network. The initial evidence suggesting that miR-34 genes are central mediators of p53 function is summarized here.
附：
Molecular Oncology (Heiko Hermeking, MPG)
The aim of our group is to understand the function and regulation of the transcription factors p53 and c-MYC, as well as the processes and genes which they regulate. c-MYC and p53 are encoded by genes which are altered in more than 50% of all cancers. The tumor suppressor gene product p53 is activated after DNA damage and induces genes, as 14-3-3sigma, which mediate cell cycle inhibition. We are studying the biology of 14-3-3sigma by structural, proteomic and genetic approaches. p53 is an integral part of a program that mediates cellular senescence and preserves genomic integrity. In contrast, activation of the c-MYC oncogene leads to immortalization and genomic instability. How these effects of oncogenic c-MYC activation are mediated is a focus of our studies. In addition, we are identifying and characterizing genetic and epigenetic alterations which contribute to prostate cancer and malignant melanoma.
