LRPPRC Promotes Colorectal Cancer Cell Invasion and Metastasis through Tumor Cell Epithelial-Mesenchymal Transition

Abstract

Background: The leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) functions to regulate cell cytoskeleton. This study assessed LRPPRC expression in colorectal cancer (CRC) for association with the clinicopathological features from patients and then investigated the impact of LRPPRC expression on CRC cells in vitro and in vivo. Material and Methods: Tissue microarrays were built using 75 cases of each really normal and CRC tissues or 75-paired normal and CRC tissues for immunohistochemical analysis of LRPPRC expression. CRC cell lines were grown and assessed for tumor cell migration and invasion using wound healing and transwell assays. Changes in mRNA and protein expression in CRC cells were assayed using western blot and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), respectively. Knockdown or overexpression of LRPPRC was conducted using siRNA and cDNA transfections, respectively. Next, a nude mouse xenograft assay was performed to verify the impact of LRPPRC expressions in vivo. Results: LRPPRC was overexpressed in CRC vs. real normal and paired normal tissues (p < 0.05), which was associated with CRC lymph node and distant metastases, and advanced clinical stages. In vitro, knockdown of LRPPRC expression inhibited CRC LOVO cell migration and invasion, whereas LRPPRC overexpression promoted CRC HCT116 cell migration and invasion. Moreover, LRPPRC overexpression upregulated Vimentin, N-cadherin, and Snail, and downregulated E-cadherin protein, whereas knockdown of LRPPRC expression had opposite results, suggesting increase in CRC cell epithelial-mesenchymal transition (EMT). In addition, knockdown of LRPPRC expression suppressed growth of colorectal cancer cell xenografts in mice. Conclusions: LRPPRC could be an oncogene or had an oncogenic activity in CRC.