耶魯大學(xué)醫(yī)學(xué)院和中國四川大學(xué)的科學(xué)家在9月7-11日的《美國科學(xué)院學(xué)報(bào)》的兩篇論文中報(bào)告說，一小段此前不知道其功能的遺傳物質(zhì)可能是制止癌癥擴(kuò)散的關(guān)鍵,。
在這些論文中,，耶魯大學(xué)分子生物物理學(xué)與生物化學(xué)系的Alan Garen和他的同事Xu Song解釋了癌癥如何能夠戰(zhàn)勝生物體的天然的細(xì)胞分裂“停止信號(hào)”,。
在早期發(fā)育階段，干細(xì)胞形成了其他細(xì)胞,，后者分化成了各種類型的組織,。隨著生物體的成熟,，新的細(xì)胞分裂和增殖停止了。然而,，癌能夠劫持這個(gè)過程,，并觸發(fā)不受控制的細(xì)胞分裂，產(chǎn)生癌腫瘤,。
制止細(xì)胞增殖的一種機(jī)制是一組腫瘤抑制蛋白（TSP）,，它們與原癌基因（即有潛力觸發(fā)癌癥的基因）結(jié)合并阻斷其功能。
Garen的研究小鼠的研究組發(fā)現(xiàn)來自基因組中并不產(chǎn)生蛋白質(zhì)的一個(gè)區(qū)域的RNA分子阻止了一種TSP關(guān)閉這些原癌基因,。他說,，他們研究的這種TSP稱為PSF，這是一種在小鼠和人類體內(nèi)幾乎一樣的蛋白質(zhì),。
耶魯大學(xué)的這個(gè)研究組通過增加PSF的量或者減少細(xì)胞中的非編碼RNA的量,，從而阻止了小鼠的腫瘤形成。
“小鼠癌癥模型的腫瘤細(xì)胞停止增殖,，腫瘤衰退,，這提示著兩種方法都可以成為一種臨床方案的基礎(chǔ)，”Garen說,。Garen也是耶魯大學(xué)癌癥中心的成員之一,。
Garen和他的同事打算繼續(xù)研究調(diào)控細(xì)胞中與PSF結(jié)合的RNA的數(shù)量的機(jī)制，他們認(rèn)為這是癌起源的關(guān)鍵,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS August 4, 2009 vol. 106 no. 31 12956-12961
Role of human noncoding RNAs in the control of tumorigenesis
Ling Lia,b,1, Tingting Fenga,1, Yingying Liana, Guangfeng Zhanga, Alan Garena,b,c,2 and Xu Songa,b,2
aCenter for Functional Genomics and Bioinformatics, College of Life Science, Sichuan University, Chengdu, Sichuan 610064, China;
bState Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; and
cDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520
Related studies showed that the protein PSF represses proto-oncogene transcription, and VL30–1 RNA, a mouse noncoding retroelement RNA, binds and releases PSF from a proto-oncogene, activating transcription. Here we show that this mechanism regulates tumorigenesis in human cells, with human RNAs replacing VL30–1 RNA. A library of human RNA fragments was used to isolate, by affinity chromatography, 5 noncoding RNA fragments that bind to human PSF (hPSF), releasing hPSF from a proto-oncogene and activating transcription. Each of the 5 RNA fragments maps to a different human gene. The tumorigenic function of the hPSF-binding RNAs was tested in a human melanoma line and mouse fibroblast line, by determining the effect of the RNAs on formation of colonies in agar and tumors in mice. (i) Expressing in human melanoma cells the RNA fragments individually promoted tumorigenicity. (ii) Expressing in human melanoma cells a shRNA, which causes degradation of the endogenous RNA from which an RNA fragment was derived, suppressed tumorigenicity. (iii) Expressing in mouse NIH/3T3 cells the RNA fragments individually resulted in transformation to tumorigenic cells. (iv) A screen of 9 human tumor lines showed that each line expresses high levels of several hPSF-binding RNAs, relative to the levels in human fibroblast cells. We conclude that human hPSF-binding RNAs drive transformation and tumorigenesis by reversing PSF-mediated repression of proto-oncogene transcription and that dysfunctional regulation of human hPSF-binding RNA expression has a central role in the etiology of human cancer.
