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microRNA促进结肠癌转移 TGF-β发挥重要作用

新药编辑:新特药 更新时间:2015-04-18

2015年4月17日讯 /tumor.net.cn/ --近日,国际学术期刊nature communication在线发表了美国康奈尔大学科学家Xiling shen研究小组的最新研究进展,他们发现microRNA-1269a能够与TGF-β形成正反馈回路,促进结肠癌转移 。

从早期癌症到晚期和转移性癌症,病人的生存率急剧下降,因此,癌症的早期诊断至关重要。研究表明可利用促进癌症复发和转移的microRNA作为诊断和预测癌症发生的生物标记,同时也可作为化疗药物的治疗靶点。

在该项研究中,研究人员发现miR-1269a能够促进结肠癌转移,并与TGF-β信号途径形成正反馈回路。MiR-1269a在晚期结肠癌中表达上调,研究人员对100名II期结肠癌病人进行长期跟踪观察发现在手术切除原发肿瘤后,miR-1269a的表达与结肠癌复发和转移具有高度相关性。与临床观察相一致,miR-1269a能够显著增强结肠癌细胞在体内侵袭和转移的能力。通过对机制研究发现,TGF-β能够通过sox4激活miR-1269a,同时miR-1269a也能够通过靶向Smad7和HOXD10增强TGF-β信号途径的活性,形成一个正反馈回路。

这一研究表明miR-1269a是能够预测结肠癌病人癌症复发和转移的生物标记,对于帮助结肠癌病人合理进行药物治疗具有重要意义,同时也是阻止癌症转移的一个潜在作用靶点。(tumor.net.cn)

miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β

Pengcheng Bu,Lihua Wang,Kai-Yuan Chen,Nikolai Rakhilin,Jian Sun,Adria Closa,Kuei-Ling Tung,Sarah King,Anastasia Kristine Varanko,Yitian Xu,Joyce Huan Chen,Amelia S. Zessin,James Shealy,Bethany Cummings,David Hsu,Steven M. Lipkin,Victor Moreno,Zeynep H. Gümü?& Xiling Shen

As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-β signalling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumours is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β signalling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.

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