Reduced expression of Dicer associated with poor prognosis in lung cancer patients.
Emerging evidence suggests that microRNA, which are well-conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let-7 was frequently reduced in lung cancers, and that reduced let-7 expression was significantly associated with shorter patient survival. Two members of the double-stranded RNA-specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non-small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P=0.001) appears to be independent of disease stage (P=0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P=0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer.
Karube
Yoko
Y
Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tanaka
Hisaaki
H
Osada
Hirotaka
H
Tomida
Shuta
S
Tatematsu
Yoshio
Y
Yanagisawa
Kiyoshi
K
Yatabe
Yasushi
Y
Takamizawa
Junichi
J
Miyoshi
Shinichiro
S
Mitsudomi
Tetsuya
T
Takahashi
Takashi
T
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D043244:Ribonuclease III / Q000235:genetics*; D012907:Smoking; D016019:Survival Analysis
D035683:MicroRNAs; C517918:DROSHA protein, human; D043244:Ribonuclease III
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