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RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients

Authors' Affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan

Requests for reprints: Hideyuki Ishiguro, Department of Surgery II, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Phone: 81-52-853-8231; Fax: 81-52-853-6440; E-mail: h-ishi{at}med.nagoya-cu.ac.jp.

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.

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