Subcellular localization of MCM2 correlates with the prognosis of ovarian clear cell carcinoma

Abstract

Highly malignant tumors overexpress the minichromosome maintenance 2 (MCM2) protein in the nucleus, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In this study, we showed that MCM2 is highly expressed in clinical samples of ovarian clear cell carcinoma. Although MCM2 expression was mainly localized to the nuclei as in other cancers, a few cases exhibited cytoplasmic localization of MCM2. Surprisingly, tumor samples with cytoplasmic MCM2 demonstrated excellent prognosis, showing 100% survival during the observation period of more than 200 months. However, cases with nuclear expression of MCM2 exhibited approximately 78% 5-year-survival rate. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound to MCM2, impaired its nuclear translocation, and enhanced DNA damage-induced apoptosis in FLV-infected hematopoietic cells with high levels of MCM2. As expected, clear cell carcinoma cells with cytoplasmic expression of MCM2 exhibited significantly higher apoptotic cell ratio than that of cells with nuclear MCM2 expression. In vitro experiments using ovarian cancer cells with cytoplasmic expression of MCM2 demonstrated that transfection of MCM2-ΔN enhanced DNA damage-induced apoptosis. Therefore, cytoplasmic localization of MCM2 significantly correlated with increased apoptosis in clear cell carcinoma cells, resulting in improved prognosis.

Changes in MCM2–7 proteins at senescence

“…Such a staining pattern may also be observed for the anti-MCM4 antibody. Our present data and other published data (Dumit et al, 2014;Aihemaiti et al, 2018) suggest that a subset of MCM2-7 proteins can be localized in the cytoplasm during interphase in higher eukaryotes, which leads to inhibition of DNA replication and cell proliferation. In higher eukaryotic cells, it is unclear whether MCM2-7 proteins shuttle between cytoplasm and nucleus during interphase, as they do in S. cerevisiae.…”

“…Recently, it has been reported that cytoplasmic localization of MCM2 is significantly correlated with increased apoptosis in clear cell carcinoma, resulting in improved prognosis (Aihemaiti et al, 2018 -Kohno et al, 2008) MCM2-related fragment (Harada et al, 2008) 63 kDa 55 kDã 110~5 00 ATP-binding Zn-finger NLS NLS Fig. 6.…”

A Novel Four-Gene Prognostic Signature as a Risk Biomarker in Cervical Cancer

“…In contrast, in our study, MCM2 played a protective role in CC progression; although consistent with previous studies [ 30 , 31 ], we also observed high expression levels of MCM2 in CC tissues. Aihemaiti et al reported that cytoplasmic rather than nuclear accumulation of MCM2 is related to improved survival for patients with ovarian clear cell carcinoma [ 32 ], which may be associated with MCM2-mediated DNA damage-induced apoptosis [ 33 , 34 ]. This pathway may also function in CC, although additional investigation is needed to explore this possibility.…”

DNA Replication Licensing Factors: Novel Targets for Cancer Therapy via Inhibiting the Stemness of Cancer Cells

“…Reduced expression of licensing factors leads to more apoptosis in different cancers. In cell lines of gastric cancer, osteosarcoma, and cervical cancer, down-regulation of CDC6 promotes cell apoptosis, which negatively impacts growth in vivo and in vitro [40][41][42]. Moreover, partial overexpression of MCMs can enhance cell proliferation significantly and suppress apoptosis, whereas knockdown of MCMs reverses these effects [43][44][45].…”