Abstract
BackgroundAs an end-proteolytic enzyme that cleaves the last three residues of proteins with a terminal CAAX, Ras-converting enzyme 1 (RCE1) has an essential role in multiple signaling pathways and take part in the process of differentiation, proliferation and carcinogenesis. The aim of the study is to investigate expression pattern of RCE1 and its prognosis in colorectal carcinoma (CRC).MethodsThe expression of RCE1 and phospho-MAPK family members was confirmed by immunohistochemical staining of CRC tissues. miR-RCE1 lentiviral vectors were transduced into HCT116 and SW489 cells. Reverse transcription PCR (RT-PCR) and western blot were conducted to measure the transfection efficiency. Transwell assays were used to detect the invasiveness of CRC cells.ResultsIn the present study, we assessed RCE1 expression in 244 CRC specimens and matching adjacent, non-tumorous tissues by immunohistochemistry (IHC). Compared with the matched adjacent non-tumor tissue samples, the RCE1 reduced in the tumor tissue samples (p < 0.001). RCE1 expression was significantly decreased in 106 of 244 (43.4%) CRC cases. In univariate and multivariate analyses, Decreasing expression of RCE1 independently predicts poor prognosis for patients in both overall survival and disease-free survival. Further study indicated that RCE1 influenced tumor invasion through the p38 pathway. Knockdown of RCE1 reduced phosphorylation and significantly increased the invasive capacity of CRC cells.ConclusionTaken together, the outcomes of this study indicate that RCE1 acts as a tumor suppressor in CRC, as its reduced expression may increase CRC cell invasion and independently predict an unsatisfactory prognosis in CRC patients.
Highlights
As an end-proteolytic enzyme that cleaves the last three residues of proteins with a terminal CAAX, Ras-converting enzyme 1 (RCE1) has an essential role in multiple signaling pathways and take part in the process of differentiation, proliferation and carcinogenesis
Our results suggested that RCE1 expression was reduced in CRC tumor tissues compared with adjacent non-tumorous tissues
Our study indicated that there was a significant difference in the local failure-free survival rate (LFFS) and distant metastasis-free survival rate (DMFS) between patients with high RCE1 expression and patients with low RCE1 expression
Summary
As an end-proteolytic enzyme that cleaves the last three residues of proteins with a terminal CAAX, Ras-converting enzyme 1 (RCE1) has an essential role in multiple signaling pathways and take part in the process of differentiation, proliferation and carcinogenesis. The aim of the study is to investigate expression pattern of RCE1 and its prognosis in colorectal carcinoma (CRC). The main function of RCE1 is to process the CAAX motifs on the C-termini of some CAAX proteins, such as the Ras superfamily of small GTPases, the the γ-subunit of heterotrimeric GTPases, nuclear lamins, several protein kinases and phosphatases [6, 7]. These proteins are involved in mulltiple processes, including differentiation and proliferation.
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