cwru获得国家卫生研究院的资助,研究lincrnas在对抗结直肠癌方面的作用。

Targeting long noncoding RNAs may offer gains compared to conventional approaches

某些编码蛋白质的基因长期以来都被认为有助于癌症的发展。但是在一个帧变换中,研究人员来自凯西储备大学医学院recently found that bepaly买球non-coding genes also contribute to the development and spreading of the disease,已知的最早的研究者这样做的例子之一。

报告这一发现的研究报告的主要作者,艾哈迈德·哈利勒,博士学位,凯斯西保留医学院遗传学和基因组科学助理教授,已被授予五年,美国国立卫生研究院提供了185万美元的资助,用于建立这一发现,最终目标是为抗癌治疗确定额外的目标。

根据新的拨款,哈利勒who is also a member of the Case Comprehensive Cancer Center,将试图了解非编码基因在结直肠癌进展中的作用。bepaly买球这些知识可以应用于设计新的疾病治疗方法,这是影响美国男性和女性的癌症中与癌症相关死亡的第二大原因。

当信使RNA(mrnas)携带细胞指令从DNA中制造蛋白质时,another class of RNAs,长非编码RNA(lincrnas)不要编码蛋白质。在来到凯斯西部保护区之前,哈利勒做出了一个开创性的发现,即人类基因组编码了数千个这些lincrna,它调节关键的手机功能,including turning coding genes on and off,细胞发育和分化,正常细胞死亡(凋亡)。"The cancer field has focused on the role of coding-RNAs and their protein products in the development of disease," said Khalil."This was,仍然是一个重要的调查领域。But in our recent research,我和我的同事已经证明,一些lincrna似乎也能帮助结肠癌细胞避免细胞死亡,而且增长速度比正常人快得多。这一发现开辟了一条平行的抗癌途径,可以显著增加克服这种令人讨厌的疾病的机会。”

以前,与正常结肠细胞相比,Khalil在肿瘤细胞中发现了超过200种不同的lincrna。One,称为lincdusp,在91%的结肠肿瘤样本中不相称地存在——在某些情况下,在正常结肠组织中超过其标准量的15倍。这有力地表明,这种以前鲜为人知的RNA形式可能参与结肠癌的形成和扩散。为了验证这个假设,Khalil and his team genetically modified colon cancer cells by depleting the amounts of lincDUSP.他们发现这些细胞开始以正常的速率复制,not the overactive rates associated with colon-cancer tumor cells.

Thus,genetically depleting the levels of lincDUSP,as well as potentially applying chemical compounds or medications to do the same job,对于结肠癌患者来说,这可能是一个富有成效的治疗机会。

"Now that we have found that lincRNAs appear to play a key role in colon cancer,我们新拨款的目标是了解它们是如何导致疾病的,这样我们就可以设计出治疗方法,”哈利勒说。“我们想了解这种形式的RNA的结构和功能。我们还将研究与细胞中其他有助于癌症发生的分子的潜在相互作用。”

Equally important,said Khalil,is that he and his team found that when they modulated the expression levels of this form of RNA in tumors removed from humans by using certain chemical compounds that bind to the RNA,长的非编码RNA降解迅速。bepaly买球These compounds haven't been previously used for cancer treatment in humans.从长远来看,哈利勒设想,通过改善传递机制,以人肿瘤中的lincrnas为靶点,可以为临床试验提供依据。In other published studies,他和他的同事们已经表明,lincrna会影响其他癌症,包括乳腺癌。lung,and melanoma.Thus,these novel approaches could have a wide impact.

"The literature on the role of long bepaly买球non-coding RNAs in colon cancer is slowly emerging with exciting possibilities," added Khalil."Under our new paradigm,using technologies that target RNA molecules,instead of proteins,在抗癌斗争中增加了一个新的维度。”

资料来源-Case Western Reserve University

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