RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients

Abstract

Purpose: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC). Experimental Design: The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR.We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated. Results: We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium. Conclusions: The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.

Post-transcriptional control of DGCR8 expression by the Microprocessor

“…Deregulation of the DGCR8 steady state level might not only be deleterious to miRNA biogenesis, but could also result in nonspecific targeting and cleavage of other RNA in cells. Altered expression of Drosha/DGCR8 has been described in cancers and shRNA-mediated depletion of Drosha or DGCR8 can lead to increased tumor cell proliferation and tumorigenicity (Lu et al 2005;Sugito et al 2006;Blenkiron et al 2007;Kumar et al 2007;Muralidhar et al 2007;Merritt et al 2008). Moreover, a widespread down-regulation of miRNA expression due to a block at the Microprocessormediated processing step has been reported in ES and cancer cells from primary tumors (Thomson et al 2006).…”

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

“…Findings in other tumour types showed decreased or increased Dicer expression associated with aggressive cancers, evoking a tissue specificity of Dicer deregulation expression in cancers. High Dicer expression was found in prostate and in oesophageal carcinomas, whereas downregulation was found in advanced lung adenocarcinoma (Chiosea et al, 2006(Chiosea et al, , 2007Sugito et al, 2006). It is noteworthy that the Dicer gene is located at the subtelomeric region 14q32.13, which carries a cluster of imprinted genes critically affected by various deletions, rearrangements, and epimutations that might potentially influence the methylation status of this region during tumour progression (Kagami et al, 2008).…”

Upregulation of Dicer is more frequent in monoclonal gammopathies of undetermined significance than in multiple myeloma patients and is associated with longer survival in symptomatic myeloma patients

“…[1][2][3][4][5][6] The potential role of Dicer and Drosha as master regulators of the RNA interference machinery in tumorigenesis has also been investigated in several malignancies. [7][8][9][10][11] Low levels of Dicer and Drosha expression were associated with advanced tumor stage and suboptimal tumor cytoreduction, respectively, in ovarian cancer. 9 Likewise, a low level of these enzymes has been found in high-risk neuroblastoma tumors with poor outcome.…”