Up-regulation of REG3A in colorectal cancer cells confers proliferation and correlates with colorectal cancer risk

Colorectal cancer (CRC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of regenerating islet-derived 3 alpha (REG3A) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of REG3A in CRC. In this study, REG3A was found elevated in CRC compared with normal tissues. Further, high REG3A expression level was correlated with bigger tumor size, poorer differentiation, higher tumor stage and lower survival rate. Knockdown of REG3A in two CRC cell lines, LOVO and RKO, significantly inhibited cell proliferation, and increased cells population in G1 phase and cell apoptotic rate. We also found that down-regulation of REG3A in CRC cells notably inhibited cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) DNA replication and base excision repair (BER) pathways were correlative with the REG3A expression, which was further confirmed in CRC cells by Western blot. Moreover, we confirmed the interaction of REG3A and fibronectin in CRC cells. We also found that there was a positive correlation between REG3A expression level and the AKT and ERK1/2 phosphorylation status. These collective data indicated that REG3A overexpression promotes CRC tumorigenesis by activating AKT and ERK1/2 pathways. REG3A may serve as a promising therapeutic strategy for CRC.