SEZ6L2 knockdown impairs tumour growth by promoting caspase-dependent apoptosis in colorectal cancer.

Seizure-related 6 homolog (mouse)-like 2 (SEZ6L2) was shown to be involved in transcription of a type 1 transmembrane protein for regulating cell fate. Until now, the expression and function of SEZ6L2 in various cancers, including colorectal cancer (CRC), were unclear. In the present study, we determined the expression of SEZ6L2 in a tissue microarray from patients with CRC and then, analysed the correlation between SEZ6L2 expression and the prognosis of the patients. Furthermore, the potential function of SEZ6L2 in CRC was determined using cell counting kit, colony formation assay and xenograft model in vitro and in vivo. Flow cytometry, Western blotting, immunohistochemical staining and a blocking experiment were employed to investigate the underlying mechanism of SEZ6L2 regulating CRC growth. Our results indicated that SEZ6L2 was significantly up-regulated in tumour tissues of patients with CRC compared with adjacent normal tissues. Up-regulation of SEZ6L2 was correlated with a poor prognosis in patients with CRC. In vitro experiments suggested that the knockdown of SEZ6L2 inhibits CRC cell growth and colony formation, but it has no significant impact on the invasion. The antitumour effects of shSEZ6L2 were also confirmed by a xenograft model. Investigations of the mechanisms indicated that the knockdown of SEZ6L2 impairs the growth of the CRC cells by inducing caspase-dependent apoptosis, which was mediated by mitochondria-related proteins. Furthermore, SEZ6L2 expression was inversely correlated with the expression of cytochrome C in malignant tissues in patients with CRC. Collectively, the present study indicates that SEZ6L2 is a potential prognosis biomarker and therapy target for CRC.