2016年6月27日，學(xué)術(shù)期刊《The Journal of Clinical Investigation》在線發(fā)表了同濟(jì)大學(xué)附屬第十人民醫(yī)院臨床醫(yī)學(xué)轉(zhuǎn)化中心、同濟(jì)大學(xué)醫(yī)學(xué)院腫瘤研究小組陸琰君教授和美國(guó)UCSD的Miles Wilkinson教授為題為“The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors”的研究論文。陸琰君教授的學(xué)生陸經(jīng)緯，蘇方和Plank Terra-Daw為共同*作者。

論文采用單細(xì)胞轉(zhuǎn)錄組技術(shù)揭示了肺假瘤形成的分子生物學(xué)的機(jī)理。該論文該研究團(tuán)隊(duì)繼2014年在《Nature Medicine》雜志發(fā)表論文后又一重要成果，該成果也是同濟(jì)大學(xué)校長(zhǎng)裴鋼院士倡導(dǎo)的現(xiàn)代轉(zhuǎn)化醫(yī)學(xué)新模式下的重大創(chuàng)新成果，基礎(chǔ)研究與臨床醫(yī)學(xué)緊密結(jié)合， 瞄準(zhǔn)臨床醫(yī)學(xué)領(lǐng)域疾病生成的關(guān)鍵科學(xué)問題，揭示了肺假瘤形成的分子生物學(xué)的機(jī)理。為揭開這個(gè)疾病的病理生里的關(guān)鍵以及zui終拿到治療這個(gè)疾病的藥物和方法打開了一個(gè)新的窗口。

<img alt="JCI:同濟(jì)大學(xué)陸琰君教授等發(fā)現(xiàn)肺假瘤形成分子生物學(xué)機(jī)理" "="" data-cke-saved-src="http://www.bio1000。。ｃｏｍ/uploads/allimg/160704/150H12600-0.png" src="http://www.bio1000。。ｃｏｍ/uploads/allimg/160704/150H12600-0.png" style="vertical-align: middle; border: 0px; width: 400px; height: 347px;">
圖解：肺假瘤形成的分子生物學(xué)的機(jī)理

原文鏈接：

The nonsense-mediated RNA decay pathway is disrupted in inflammatory myofibroblastic tumors

原文摘要：

Inflammatory myofibroblastic tumors (IMTs) are characterized by myofibroblast proliferation and an inflammatory cell infiltrate. Little is known about the molecular pathways that precipitate IMT formation. Here, we report the identification of somatic mutations in UPF1, a gene that encodes an essential component of the nonsense-mediated RNA decay (NMD) pathway, in 13 of 15 pulmonary IMT samples. The majority of mutations occurred in a specific region of UPF1 and triggered UPF1 alternative splicing. Several mRNA targets of the NMD pathway were upregulated in IMT samples, indicating that the UPF1 mutations led to reduced NMD magnitude. These upregulated NMD targets included NIK mRNA, which encodes a potent activator of NF-κB. In human lung cells, UPF1 depletion increased expression of chemokine-encoding genes in a NIK-dependent manner. Elevated chemokines and IgE class switching events were observed in IMT samples, consistent with NIK upregulation in these tumors. Together, these results support a model in which UPF1 mutations downregulate NMD, leading to NIK-dependent NF-κB induction, which contributes to the immune infiltration that is characteristic of IMTs. The molecular link between the NMD pathway and IMTs has implications for the diagnosis and treatment of these tumors.

doi:10.1172/JCI86508.

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