Abstract
Colon cancer (CC) is one of the major malignancies worldwide, whose pathogenesis is complex and requires the accumulated alteration of multiple genes and signaling pathways. Condensins are multi-protein complexes that play pivotal roles in chromosome assembly and segregation during mitosis, meiosis and even tumorigenesis. Using tissue microarrays by immunohistochemistry and hematoxylin–eosin staining, we found that non-SMC condensin I complex subunit H (NCAPH) in colon cancerous tissues was higher than that in all corresponding adjacent non-cancerous tissues. We then characterized the exact function of the NCAPH in CC. We provided evidences showing that NCAPH is highly expressed in colorectal cancer cell lines comparing with normal human colonic epithelial cells, and identified many NCAPH mutations in CC patients. We found that depletion of NCAPH inhibits CC cell proliferation, migration in vitro and xenograft tumor formation in vivo. Furthermore, NCAPH knockdown promotes cell apoptosis and cell cycle arrest at G2/M phase. Interestingly, the NCAPH high expression in tumor tissues of colon patients had a significantly better prognosis and survival rate than low-expression patients, suggesting that NCAPH high expression promotes colonic cancerous cell proliferation; on the other hand, it may also sensitize these cells responding to chemo- or radio-therapies. Collectively, these findings reveal an important role of NCAPH in CC, indicating that NCAPH could be used as a new therapeutic target in future.
Highlights
Condensins I and II share the same pair of core subunits, CAP-E/SMC2 and CAP-C/SMC4, both belonging to a large family of chromosomal ATPases, the SMC family whose members are involved in many aspects of higher-order chromosome dynamic, and three different non-SMC subunits.[10,11,12]
Former findings demonstrated that the homologs of Xenopus condensin subunits, barren-1/ hCAP-H, hCAP-C, hCAP-E, CNAP1 and hCAP-G form a heteropentamer capable of inducing chromosome condensation in the Xenopus egg extract model.[26]
The human homolog of XCAP-H/barren, named hCAP-H, and it is mapped to 2q11.2.27
Summary
Colon cancer (CC) is one of the most common malignancies and the leading cause of cancer-related mortality among both men and women worldwide, which accounts for roughly 1.2 million new cases and 600 000 deaths per year.[1,2,3,4] The highest incidence has been reported in countries of Europe and North America, rapid increases in low-risk countries, such as in eastern Europe and east Asia, have recently been documented, which resulted from changes in dietary patterns and risk factors towards a so-called western lifestyle.[4,5] The prognosis of patients with CC has been improved during the past decades in many countries, its invasion and metastasis is one of the biggest problems in the clinical treatment, and is the most common reason for treatment failure. Non-SMC condensin I complex subunit H (NCAPH) is one of the three non-SMC subunits in condensin I, which belongs to a recently defined superfamily of proteins termed kleisins.[13] Another two non-SMC subunits, CAP-D2 and CAP-G, share a highly degenerate repeating motif known as HEAT repeat.[14] Some studies show that each subunit is essential for viability and plays an important role in mitotic chromosome. Our findings indicate a critical role of NCAPH gene in the cure and prognosis of CC, which provide a possible new direction for CC research
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