Reduced expression of Dicer associated with poor prognosis in lung cancer patients

Abstract

Emerging evidence suggests that microRNA, which are wellconserved, 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).

MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers

“…Micheal et al reported that mirs-143 and -145 consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal cancers and that in cancer cells decreased levels of mature miRNAs was due to reduced Dicer-processing activity. In our study, since the introduction of mir-143 or -145 precursors into the DLD-1 and SW480 cells caused growth inhibition, the activity and expression of Dicer and RNA-induced silencing complex (RISC) proteins which exert the enzymatic modification of precursor miRNAs seemed to be intact (16)(17)(18). Therefore, we propose that the cause of inadequate expression of mirs-143 and -145 was due to the perturbation of transcription and/or the enzymatic process of the transition from primary miRNAs to precursor ones including Drosha and DGCR8, events that occur in the nucleus (16,17).…”

Methylation of Human MicroRNA Genes in Normal and Neoplastic Cells

“…11,12 Reduced expression of Dicer also has been shown to be involved in lung cancer and is associated with a reduced life span of cancer patients. 13 While the majority of miRNA genes seem to be downregulated in cancer (see below), some miRNAs tend to be upregulated. Human B cell lymphomas, for example, show elevated levels of miR-155, which is derived from the nonprotein-coding transcript of the proto-oncogene BIC.…”

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

“…They have been found to have roles in cell growth, differentiation, apoptosis and tumourigenesis. [7][8][9][10][11][12][13][14] Furthermore, unique microRNA expression profiles have been able to classify various cancers. Recently, microRNAs were implicated in the development of ovarian cancer: 39 microRNAs are differentially regulated between tumour and normal ovarian tissue.…”