10%到15%的肺癌发生在从不吸烟的人身上。此前的研究发现了所谓从不吸烟者的肺癌和吸烟者的肺癌之间具有遗传和临床上的差异。例如，一个称为EGFR基因的突变在从不吸烟者身上比在吸烟者身上更常见。对于一些拥有EGFR突变的患者，称为EGFR-TKIs的药物有效。然而，至多30%的EGFR突变肺癌病例对这种药物没有反应，因此需要新的治疗靶标。科学家已经越来越多地把一类称为微RNA（miRNA）的小分子浓度的变化与各种类型的人类癌症联系了起来。
Masahiro Seike及其同事调查了从不吸烟的肺癌患者的miRNA，并把它们和吸烟的肺癌患者的miRNA进行了比较。这组科学家还比较了拥有EGFR突变的肺癌和没有这些突变的肺癌的miRNAs。这组作者发现了一种称为miR-21的miRNA在吸烟和不吸烟的肺癌患者体内显著增加，而EGFR突变让miR-21浓度进一步增加。当这组作者在离体肺癌细胞中阻断了miR-21的时候，这些细胞死亡了。这组作者说，miR-21可能成为未来癌症治疗的一个宝贵的靶标。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
