癌症、糖尿病和生活方式有多大关系?表观遗传学研究让我们大吃一惊

2016-04-18 应雨妍 奇点网

不管是否研究生物,孟德尔这个名字对于读者朋友们一定不会陌生,估计他应该是很多朋友们中学时代在生物学科上的一个噩梦吧。孟德尔是伟大的生物学家,他用豌豆奠定了自己“遗传学之父”的地位。和他相比,另一位搞遗传学的科学家拉马克则可以说是光景惨淡。在19世纪初,拉马克大胆地提出了“用进废退,获得性遗传”的概念,但在孟德尔的“中心法则”被确定了经典遗传学界的指导性地位后,与它相悖的“拉马克学说”就被世人所

不管是否研究生物,孟德尔这个名字对于读者朋友们一定不会陌生,估计他应该是很多朋友们中学时代在生物学科上的一个噩梦吧。

孟德尔是伟大的生物学家,他用豌豆奠定了自己“遗传学之父”的地位。和他相比,另一位搞遗传学的科学家拉马克则可以说是光景惨淡。在19世纪初,拉马克大胆地提出了“用进废退,获得性遗传”的概念,但在孟德尔的“中心法则”被确定了经典遗传学界的指导性地位后,与它相悖的“拉马克学说”就被世人所摒弃了。

近年来,在表观遗传学的概念被炒热之后,不少人开始思考,表观遗传将来是否可以为拉马克正名呢?虽然这个答案还不得而知,但是在这之前,先提一个问题,大家真的明白“表观遗传”四个字背后代表着什么吗?

表观遗传学,顾名思义,DNA序列不发生改变,但是在基因表达上产生了可遗传的变异。也就是说,在细胞内,除去遗传信息外,其他的一些遗传物质发生了变异,并且稳定地遗传给了后代。

所以,你有没有想过,你的一些生活习惯,不仅会影响你自己的健康,还有可能改变你的遗传物质,而且影响你的后代呢?


•表观遗传与肥胖

前面说的很”玄”的话并不是危言耸听哟,如果父母是高脂食物的爱好者,那么生出来的小朋友更有可能患糖尿病和肥胖。这在过去是人们所不敢想的一件事(当然,除了不敢想,也可能是有人为了自己不健康的生活方式找借口不愿意承认呢)。

实验人员将小鼠父母分为高脂组、中脂组和低脂组,在高脂组出现肥胖和葡萄糖耐受能力下降后,提取精子与卵子,体外受精成功后把受精卵转移进健康的代孕母鼠体内,在三组的小鼠宝宝出生后,再喂食高脂食物时,高脂组的鼠宝宝相对于其他两组的体重增长和葡萄糖耐受紊乱症状都明显严重。这算是表观遗传的一项直接证据,解释了环境的改变多少能够改变我们的遗传信息。[1]

•表观遗传与糖尿病

我们知道,糖尿病分为先天与后天发病的,后天发病的为2型糖尿病,2型糖尿病一直被认为是多基因遗传病,但是2014年的一项研究表明,罹患2型糖尿病的风险不仅是遗传学问题,而且涉及到表观遗传学。

研究人员对健康人群和2型糖尿病患者的胰岛素生产细胞,进行了全基因组DNA甲基化图谱分析。分析结果表明,在2型糖尿病患者中,大约800个基因中具有表观遗传学变化。超过100个基因的表达也发生了改变,这些基因中一大部分可导致胰岛素的分泌减少。这是2型糖尿病发病的一个内在原因。这项研究结果除了能帮助我们理解2型糖尿病的发病机制之外,也为将来治疗药物的开发提供了新的思路。[2]

•表观遗传与癌症

一直以来,人们都没有把癌症和表观遗传联系在一起,但是在去年的一项研究中,研究人员发现了表观遗传和乳腺癌干细胞之间的联系。

哺乳动物在怀孕和泌乳期,乳腺干细胞能够维持乳腺上皮组织的自我更新。在自我更新过程中,DNA甲基化为维持细胞记忆提供了潜在的表观遗传机制。而DNA甲基化所需的甲基转移酶DNMT1在乳腺干细胞和癌症干细胞维持方面具有重要作用,同时DNMT1靶基因的过表达也可抑制乳腺肿瘤生长。[3]

除了与癌症的潜在联系外,表观遗传对癌症的治疗也有着非常可观的前景。在去年的时候,就有科学家发现,在治疗两种突变型非小细胞肺癌时,化疗起不到效果,而在常用化疗药物的基础上加入表观遗传学药物后,治疗效果有了很大提高。[4]

表观遗传如此的神奇,它的机制自然也是科学家们一直所探寻的。最开始被发现的大家就是甲基化作用了,它的作用就像是一个帽子,带上它,基因关闭;脱掉它,基因表达。除此之外,就是组蛋白途径和微小RNA(microRNA)了。对它的机制的研究势必也会和应用一样,不断地向前发展。

未来

在上个月,一向眼光独到、对生命科学界非常看好的谷歌风投也在表观遗传学领域开辟了自己的“地盘”,谷歌风投作为主投资人,联合其他几家投资机构将2100万美元投给了Cambridge Epigenetix(CEGX)公司。

这家公司最初是在剑桥大学“孕育”出来的,他们的主要开发方向为表观遗传学测序技术。根据现有的研究,很多癌症、自发免疫性疾病和神经性病变都可能由异常的表观遗传学变化引起,而治疗方法的灵感可能来自于“关闭”相应的异常基因。

由此可见,表观遗传学在癌症等疑难杂症的治疗上会占据非常大的市场份额,所以,现在除了CEGX,也有一些公司将目光放在了这个市场上,例如Celgene公司就是他们中的佼佼者。然而根据业内人士的估计,未来的10年内,CEGX的表观遗传学治疗方法会占领一大部分癌症领域的市场份额。

继基因组测序走上商业化道路后,表观遗传学也有希望成为资本争相追逐的一个科学技术发展的方向。所以,我们可以预见的是,表观遗传有着不可限量的前途,等待科学家们去开发探索。

参考文献:

[1] HuypensP, Sass S, Wu M, et al. Epigenetic germline inheritance of diet-induced obesityand insulin resistance[J]. Nature genetics, 2016.

[2] DayehT, Volkov P, Salö S, et al. Genome-wide DNA methylation analysis of humanpancreatic islets from type 2 diabetic and non-diabetic donors identifiescandidate genes that influence insulin secretion[J]. PLoS Genet, 2014, 10(3):e1004160.

[3] Rajneesh Pathania, Sabarish Ramachandran etal.DNMT1 is essential for mammary and cancer stem cell maintenance andtumorigenesis. Nature Communications, April 24, 2015; doi:10.1038/ncomms7910.

[4] FillmoreC M, Xu C, Desai P T, et al. EZH2 inhibition sensitizes BRG1 and EGFR mutantlung tumours to TopoII inhibitors[J]. Nature, 2015, 520(7546): 239-242.

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    2016-05-02 1de4921fm57(暂无匿称)

    世事无绝对我觉得两个都对又不冲突

    0

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    2016-04-19 1dea6088m20(暂无匿称)

    公认2型糖尿病有遗传倾向该文又架起了环境饮食因素和表观遗传的桥联比较合乎实际的狀况

    0

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    2016-04-19 李继凯

    学习了…

    0

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    2016-04-19 李继凯

    改变生活习惯

    0

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    2016-04-18 ssummer

    已阅!

    0

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    2016-04-18 wei834766788

    很多疾病是???

    0

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