耶鲁大学医学院和中国四川大学的科学家在9月7-11日的《美国科学院学报》的两篇论文中报告说，一小段此前不知道其功能的遗传物质可能是制止癌症扩散的关键。
在这些论文中，耶鲁大学分子生物物理学与生物化学系的Alan Garen和他的同事Xu Song解释了癌症如何能够战胜生物体的天然的细胞分裂“停止信号”。
在早期发育阶段，干细胞形成了其他细胞，后者分化成了各种类型的组织。随着生物体的成熟，新的细胞分裂和增殖停止了。然而，癌能够劫持这个过程，并触发不受控制的细胞分裂，产生癌肿瘤。
制止细胞增殖的一种机制是一组肿瘤抑制蛋白（TSP），它们与原癌基因（即有潜力触发癌症的基因）结合并阻断其功能。
Garen的研究小鼠的研究组发现来自基因组中并不产生蛋白质的一个区域的RNA分子阻止了一种TSP关闭这些原癌基因。他说，他们研究的这种TSP称为PSF，这是一种在小鼠和人类体内几乎一样的蛋白质。
耶鲁大学的这个研究组通过增加PSF的量或者减少细胞中的非编码RNA的量，从而阻止了小鼠的肿瘤形成。
“小鼠癌症模型的肿瘤细胞停止增殖，肿瘤衰退，这提示着两种方法都可以成为一种临床方案的基础，”Garen说。Garen也是耶鲁大学癌症中心的成员之一。
Garen和他的同事打算继续研究调控细胞中与PSF结合的RNA的数量的机制，他们认为这是癌起源的关键。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
