Science：ncRNA关键酶与癌症

　　

生物通报道，华盛顿大学医学中心，明尼苏达大学儿童医院，威斯康辛儿童医院，辛辛那提儿童医院的研究者在最新一期的Science发表DICER1 Mutations in Familial Pleuropulmonary Blastoma文章，解析了一种影响非编码RNA合成的酶对一种罕见癌症的作用。

 

这种罕见的癌症是：胸膜肺母细胞瘤(pleuropulmonary blastoma，PPB)，是一种少见的肺胚胎发育异常性恶性肿瘤。小儿PPB的临床表现无特异性，患儿绝大多数于6岁以内发病，平均3.2岁，男女发病无明显差异，约25%病人有家族史。小儿PPB其主要症状常为反复咳嗽、发热等呼吸道症状，抗炎治疗无效。胸部X线和CT的常表现为在肺周边部的巨大团块，可以是囊性、实性或囊实性，右侧多见，伴有胸腔积液、脓胸；纵隔向健侧移位；胸壁无侵犯。小儿PPB的诊断主要依靠病理形态表现，手术完整切出是治疗的关键。

 

D. Ashley Hill研究小组对11个有PPB家族遗传史的患者进行遗传学分析，筛选出一个与PPB发生相关的基因突变。

 

研究发现DICER1基因发生突变导致DICER1蛋白功能丧失可能导致肿瘤的生成。DICER1是一种核糖核酸酶，它具有帮助细胞生成调节性非编码RNA（如miRNAs）的功能。

 

一旦胎儿肺脏发育过程中DICER1丧失功能则可能改变调控基因表达的ncRNA的转录，从而影响正常的发育，导致癌症的发生。

（生物通  小茜）

生物通推荐原文检索：

DICER1 Mutations in Familial Pleuropulmonary Blastoma

 

D. Ashley Hill 1*, J. Ivanovich 2, John R. Priest 3, Christina A. Gurnett 2, Louis P. Dehner 2, David Desruisseau 2, Jason A. Jarzembowski 4, Kathryn A. Wikenheiser-Brokamp 5, Brian K. Suarez 2, Alison J. Whelan 2, Gretchen Williams 6, Dawn Bracamontes 1, Yoav Messinger 6, Paul J. Goodfellow 2

1 Washington University Medical Center, St. Louis, MO 63110, USA.; The International Pleuropulmonary Blastoma Registry, Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.

2 Washington University Medical Center, St. Louis, MO 63110, USA.

3 The International Pleuropulmonary Blastoma Registry, Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.

4 Children’s Hospital of Wisconsin, Milwaukee, WI 53201, USA.

5 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

6 The International Pleuropulmonary Blastoma Registry, Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.; Children’s Hospitals and Clinics of Minnesota, Minneapolis, MN 55404, USA.

 

【Abstract】

Pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that is often part of an inherited cancer syndrome. PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation. Here, we show that 11 multiplex PPB families harbor heterozygous germline mutations in DICER1, a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs. Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma). We hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.