10%到15%的肺癌發(fā)生在從不吸煙的人身上,。此前的研究發(fā)現(xiàn)了所謂從不吸煙者的肺癌和吸煙者的肺癌之間具有遺傳和臨床上的差異。例如,，一個(gè)稱為EGFR基因的突變?cè)趶牟晃鼰熣呱砩媳仍谖鼰熣呱砩细Ｒ姟?duì)于一些擁有EGFR突變的患者,，稱為EGFR-TKIs的藥物有效,。然而，至多30%的EGFR突變肺癌病例對(duì)這種藥物沒(méi)有反應(yīng),，因此需要新的治療靶標(biāo),。科學(xué)家已經(jīng)越來(lái)越多地把一類稱為微RNA（miRNA）的小分子濃度的變化與各種類型的人類癌癥聯(lián)系了起來(lái),。
Masahiro Seike及其同事調(diào)查了從不吸煙的肺癌患者的miRNA,，并把它們和吸煙的肺癌患者的miRNA進(jìn)行了比較。這組科學(xué)家還比較了擁有EGFR突變的肺癌和沒(méi)有這些突變的肺癌的miRNAs,。這組作者發(fā)現(xiàn)了一種稱為miR-21的miRNA在吸煙和不吸煙的肺癌患者體內(nèi)顯著增加,，而EGFR突變讓miR-21濃度進(jìn)一步增加。當(dāng)這組作者在離體肺癌細(xì)胞中阻斷了miR-21的時(shí)候,，這些細(xì)胞死亡了,。這組作者說(shuō)，miR-21可能成為未來(lái)癌癥治療的一個(gè)寶貴的靶標(biāo),。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS July 13, 2009, doi: 10.1073/pnas.0905234106
MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers
Masahiro Seikea,b, Akiteru Gotoa, Tetsuya Okanoa,b, Elise D. Bowmana, Aaron J. Schettera, Izumi Horikawaa, Ewy A. Mathea, Jin Jenc, Ping Yangd, Haruhiko Sugimurae, Akihiko Gemmab, Shoji Kudohb, Carlo M. Crocef,1 and Curtis C. Harrisa,1
Fifteen percent of lung cancer cases occur in never-smokers and show characteristics that are molecularly and clinically distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and unidentified (e.g., down-regulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs, including miR-21, were more remarkable in cases with EGFR mutations than in those without these mutations. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggest that the EGFR signaling is a pathway positively regulating miR-21 expression. In the never-smoker–derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker–derived adenocarcinoma cell line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is enhanced further by the activated EGFR signaling pathway, plays a significant role in lung carcinogenesis in never-smokers, as well as in smokers, and is a potential therapeutic target in both EGFR-mutant and wild-type cases.
