Science子刊:生物钟紊乱可直接加速结直肠癌进展!

2022-08-16 转化医学网 转化医学网

他们还证明了环境对生物钟的破坏会加速APC突变,从而增加了GEMM小鼠模型中的肿瘤负担。

导读:据报道,年轻人患结直肠癌(CRC)的机率呈现惊人增长趋势;然而,其潜在的分子机制仍未定义。幼发性结直肠癌的疑似危险因素包括环境因素,如生活方式和饮食习惯,均会影响生物钟。在一项新的研究中,研究人员确定了生物钟如何影响细胞生长,代谢和肿瘤进展。他们的研究还揭示了生物钟的破坏如何影响基因组的稳定性和突变,从而进一步驱动肠道中的关键肿瘤发展。

这项研究的标题是“Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer”,于8月10日发表在《Science Advances》杂志上。

https://www.science.org/doi/10.1126/sciadv.abo2389

研究背景

01

根据美国国立卫生研究院的数据,年轻人中早发性结直肠癌的发病率出现了惊人的上升。今天,近10%的CRC病例现在在50岁以下的人群中被诊断出来,而且这一趋势正在稳步上升。可疑的危险因素包括环境因素,如生活方式和饮食因素,已知会影响生物钟。

“作为一个社会,我们长期暴露于影响我们生物钟的几个环境因素下,包括夜班工作,长时间的光照,睡眠/觉醒周期的变化和喂养行为的改变,”UCI医学院生物化学助理教授Selma Masri博士说。“令人震惊的是,我们已经看到几种年轻发病的癌症,包括结直肠癌,出现了惊人的增长。20多岁和30多岁成年人癌症发病率增加的根本原因仍未确定。然而,根据我们的发现,我们现在认为生物钟的紊乱起着重要作用。

研究进展

02

在研究过程中,科学家们开发了一种新的组织特异性基因工程小鼠模型(GEMM)来定义连接昼夜节律破坏和CRC发病机制的分子途径。研究结果表明,与单独使用Apc的破坏相比,肠道Apc和Bmal1的遗传缺失导致息肉形成在统计学上显著增加。他们还证明了环境对生物钟的破坏会加速APC突变,从而增加了GEMM小鼠模型中的肿瘤负担。

研究结果

03

在这项研究中,研究人员发现,生物钟的遗传破坏和环境破坏都有助于腺瘤性息肉病大肠杆菌(APC)肿瘤抑制因子的突变,该抑制因子在绝大多数人类结直肠癌(CRC)中发现。在大约80%的人类CRC病例中报告了APC点突变,缺失和杂合性(LOH)事件,正是这些突变推动了肠腺瘤发展的开始。

APC突变也与关键致癌途径(包括Kras,Braf,p53和Smad4)中的第二次命中有关,这些突变驱动腺癌进展,共同促进疾病进展。这些发现现在涉及生物钟的破坏,以驱动额外的基因组突变,这些突变对加速结直肠癌至关重要。

研究意义

04

生物钟是一种内部生物起搏器,控制着许多生理过程。马斯里实验室的研究主要集中在生物钟的破坏如何参与某些癌症类型的发展和进展。接下来,研究人员将继续开展进一步的研究,旨在确定生物钟如何影响其他癌症类型。

参考资料:

https://phys.org/news/2022-08-reveals-circadian-clock-cell-growth.html

https://www.science.org/doi/10.1126/sciadv.abo2389

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1243213, encodeId=1396124321390, content=<a href='/topic/show?id=6a3c69486e3' target=_blank style='color:#2F92EE;'>#生物钟#</a>紊乱可直接加速<a href='/topic/show?id=493ae869206' target=_blank style='color:#2F92EE;'>#结直肠癌#</a>进展,应该是所有的<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69486, encryptionId=6a3c69486e3, topicName=生物钟), TopicDto(id=78692, encryptionId=493ae869206, topicName=结直肠癌), TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=小小医者, createdTime=Mon Sep 05 02:07:41 CST 2022, time=2022-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376497, encodeId=8d7613e6497d0, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453739, encodeId=62f41453e39da, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239135, encodeId=4b5c1239135b0, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Tue Aug 16 22:32:07 CST 2022, time=2022-08-16, status=1, ipAttribution=)]
    2022-09-05 小小医者

    #生物钟#紊乱可直接加速#结直肠癌#进展,应该是所有的#肿瘤#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1243213, encodeId=1396124321390, content=<a href='/topic/show?id=6a3c69486e3' target=_blank style='color:#2F92EE;'>#生物钟#</a>紊乱可直接加速<a href='/topic/show?id=493ae869206' target=_blank style='color:#2F92EE;'>#结直肠癌#</a>进展,应该是所有的<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69486, encryptionId=6a3c69486e3, topicName=生物钟), TopicDto(id=78692, encryptionId=493ae869206, topicName=结直肠癌), TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=小小医者, createdTime=Mon Sep 05 02:07:41 CST 2022, time=2022-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376497, encodeId=8d7613e6497d0, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453739, encodeId=62f41453e39da, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239135, encodeId=4b5c1239135b0, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Tue Aug 16 22:32:07 CST 2022, time=2022-08-16, status=1, ipAttribution=)]
    2022-08-18 jichang
  3. [GetPortalCommentsPageByObjectIdResponse(id=1243213, encodeId=1396124321390, content=<a href='/topic/show?id=6a3c69486e3' target=_blank style='color:#2F92EE;'>#生物钟#</a>紊乱可直接加速<a href='/topic/show?id=493ae869206' target=_blank style='color:#2F92EE;'>#结直肠癌#</a>进展,应该是所有的<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69486, encryptionId=6a3c69486e3, topicName=生物钟), TopicDto(id=78692, encryptionId=493ae869206, topicName=结直肠癌), TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=小小医者, createdTime=Mon Sep 05 02:07:41 CST 2022, time=2022-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376497, encodeId=8d7613e6497d0, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453739, encodeId=62f41453e39da, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239135, encodeId=4b5c1239135b0, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Tue Aug 16 22:32:07 CST 2022, time=2022-08-16, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1243213, encodeId=1396124321390, content=<a href='/topic/show?id=6a3c69486e3' target=_blank style='color:#2F92EE;'>#生物钟#</a>紊乱可直接加速<a href='/topic/show?id=493ae869206' target=_blank style='color:#2F92EE;'>#结直肠癌#</a>进展,应该是所有的<a href='/topic/show?id=aa0582e6946' target=_blank style='color:#2F92EE;'>#肿瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69486, encryptionId=6a3c69486e3, topicName=生物钟), TopicDto(id=78692, encryptionId=493ae869206, topicName=结直肠癌), TopicDto(id=82769, encryptionId=aa0582e6946, topicName=肿瘤)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=小小医者, createdTime=Mon Sep 05 02:07:41 CST 2022, time=2022-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376497, encodeId=8d7613e6497d0, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453739, encodeId=62f41453e39da, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Thu Aug 18 01:30:05 CST 2022, time=2022-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1239135, encodeId=4b5c1239135b0, content=认真学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Tue Aug 16 22:32:07 CST 2022, time=2022-08-16, status=1, ipAttribution=)]
    2022-08-16 医鸣惊人

    认真学习了

    0

相关资讯

Nature Chemical Biology:结直肠癌治疗新靶点——ALDH1B1

结直肠癌(Colorectal Cancer,CRC)是全世界范围内发病率第三的癌症,每年新增发病人数近200万(仅次于乳腺癌和肺癌),每年导致的死亡人数接近100万(仅次于肺癌)。

精彩直播:2022CSCO结直肠癌专家委员会年会

整合解读结直肠癌最新治疗方案

CGH: 慢性便秘是结直肠癌的危险因素

慢性便秘表现为排便次数减少、粪便干硬和(或)排便困难。患者每周排便少于3次,排便费力、排出困难或有排便不尽感,病程至少6个月。

“免疫双子星”布局结直肠癌辅助、后线治疗战力拉满!快看CRC新进展~

就研究中观察到的总体 AE 而言,高血压是最常见的 3 级或更高级别的 AE(7.0%)。

Lancet Regional Health:通过筛查检出的结直肠癌患者的生存率

通过筛查检出的结直肠癌患者的预后都非常好

Nature Cancer:类器官研究揭开结直肠癌化疗后易复发的关键

化疗通常被用于结直肠癌的治疗,而且在最初的治疗中是有效的,但大多数患者在化疗后会出现病情复发。