RRP12 suppresses cell migration and invasion in colorectal cancer cell via regulation of epithelial-mesenchymal transition.

ABSTRACT

Background: The survival of patients with advanced colorectal cancer (CRC) is variable. The high rates of recurrence, metastasis, and drug resistance make clinical treatment difficult, which needs to further develop therapeutic and prognostic targets. Ribosomal RNA processing 12 homolog (RRP12), as a nucleolar protein involved in ribosome subunit maturation and export, plays important roles in cell cycle-related processes and the response to DNA damage, and regulates the occurrence and development of various cancers. The primary aim of this study was to identify the function of RRP12 in the process of epithelial-mesenchymal transition (EMT) in CRC. Methods: In this study, the expression of RRP12 in tissue samples and the association with clinicopathological features in CRC was evaluated, and the correlation between RRP12 expression and aggressiveness of CRC was detected. After knockdown of RRP12 gene, the relationship between RRP12 and EMT-related indicators was verified in vivo and in vitro of CRC cells. Identification of RRP12-related genes and pathways through bioinformatic-based analyses was performed to find its potential mechanism. Results: RRP12 is highly expressed in CRC cell lines and clinical samples and is associated with poor survival in CRC patients. RRP12 expression was positively associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and poor differentiation. Knockdown of RRP12 was found to suppress migration and invasion of CRC cells. RRP12 contributed to the EMT process of CRC cell lines in a ZEB1-mediated manner. RRP12 knockdown was found to reverse metastasis of CRC cells in vivo. Bioinformatic-based analyses indicated that RRP12 could serve as a potential biomarker for prognostic assessment of CRC patients. Conclusions: RRP12 is involved in the tumorigenesis and metastasis of CRC by regulating the EMT process through ZEB1. Thus, RRP12 could be a potential therapeutic target for CRC therapy.