Urocortin-1 promotes colorectal cancer cell migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway

Purpose To investigate the effect of urocortin-1 (UCN-1) on growth, migration, and apoptosis in colorectal cancer (CRC) in vivo and vitro and the mechanism by which UCN-1 modulates CRC cells in vitro.

Methods The correlation between UCN-1 and CRC was evaluated using The Cancer Genome Atlas (TCGA) database and a tissue microarray.

The expression of UCN-1 in CRC cells was assessed using quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting.

In vitro, the influence of UCN-1 on the proliferation, apoptosis, and migration of HT-29, HCT-116, and RKO cells was explored using the celigo cell counting assay or cell counting kit-8 (CCK8), flow cytometry, and wound healing or Transwell assays, respectively.

In vivo, the effect of UCN-1 on CRC growth and progression was evaluated in nude mice.

The downstream pathway underlying UCN-1-mediated regulation of CRC was determined using the phospho-kinase profiler array in RKO cells.

Lentiviruses were used to knockdown or upregulate UCN-1 expression in cells.

Results Both the TCGA and tissue microarray results showed that UCN-1 was strongly expressed in the tissues of patients with CRC.

Furthermore, the tissue microarray results showed that the expression of UCN-1 was higher in male than in female patients, and high expression of UCN-1 was associated with higher risk of lymphatic metastasis and later pathological stage.

UCN-1 knockdown caused a reduction in CRC cell proliferation, migration, and colony formation, as well as an increase in apoptosis.

In xenograft experiments, tumors generated from RKO cells with UCN-1 knockdown exhibited reduced volumes and weights.

A reduction in the expression of Ki-67 in xenograft tumors indicated that UCN-1 knockdown curbed tumor growth.

The human phospho-kinase array showed that the p53 signaling pathway participated in UCN-1-mediated CRC development.

The suppression in migration and proliferation caused by UCN-1 knockdown was reversed by inhibitors of p53 signal pathway, while the increase in cell apoptosis was suppressed.

On the other hand, overexpression of UCN-1 promoted proliferation and migration and inhibited apoptosis in CRC cells.

Overexpression of p53 reversed the effect of UCN-1 overexpression on CRC development.

Conclusion UCN-1 promotes migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.