High Expression of Orail Enhances Cell Proliferation and is Associated with Poor Prognosis in Human Colorectal Cancer

Background: Store-operated Ca2+ entry (SOCE) is the predominant Ca2+ influx mechanism in non-excitable cells and regulates a variety of cellular functions. As the essential channel pore-forming protein of SOCE, Orail has recently been implicated in carcinogenesis and tumor progression in multiple malignancies. However, the role of Orail in colorectal cancer (CRC) has not been investigated. Methods: The expression of Orail in 21 CRC specimens was examined by immunohistochemistry (IHC) staining, Western blot, and qRT-PCR. The results were compared with paired non-tumor tissues. The expression of Orail in additional specimens of 129 CRC patients was examined by IHC staining and the IHC scores were compared with clinicopathological features. After knock-down of the expression of Orail in LoVo cells, cell proliferation was examined using a MTT assay and colony formation assay. Flow cytometry was also used to detect apoptosis. Results: The expression of Orail was upregulated in human CRC tissues, high expression of Orail was closely associated with depth of tumor invasion, lymph node metastasis, and perineural invasion, and patients with high expression of Orail had shorter overall survival. Moreover, the expression of Orail was also upregulated in CRC cell lines, knockdown of Orail inhibited cell proliferation, the effect of growth inhibition was not due to enhanced apoptosis, and stromal interaction molecule1 (STIM1) did not take part in the regulation of CRC cell proliferation. Conclusions: Orail is crucial to sustained CRC cell proliferation, high expression of Orail is associated with tumor progression and poor prognosis, and Orail may be a promising target for prognosis and treatment of CRC.