Dataset Information

Nuclear division cycle 80 promotes malignant progression and predicts clinical outcome in colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is a common human malignancy worldwide and increasing studies have attributed its malignant progression to abnormal molecular changes in cancer cells. Nuclear division cycle 80 (NDC80) is a newly discovered oncoprotein that regulates cell proliferation and cycle in numerous malignancies. However, its clinical significance and biological role in CRC remain unclear. Therefore, in this study, we firstly analyze its expression in a retrospective cohort enrolling 224 CRC patients and find its overexpression is significantly correlated with advanced tumor stage and poor prognosis in CRC patients. In addition, our result reveals it is an independent adverse prognostic factor affecting CRC-specific and disease-free survival. The subgroup analysis indicates NDC80 expression can stratify the clinical outcome in stage II and III patients, but fails in stage I and IV patients. In cellular assays, we find knockdown of NDC80 dramatically inhibits the proliferative ability, apoptosis resistance, cell cycle progression, and clone formation of CRC cells in vitro. Using xenograft model, we further prove knockdown of NDC80 also inhibits the tumorigenic ability of CRC cells in vivo. Finally, the microarray analysis is utilized to preliminarily clarify the oncogenic molecular mechanisms regulated by NDC80 and the results suggest it may promote CRC progression partly by downregulating tumor suppressors such as dual specificity phosphatase 5 and Forkhead box O1. Taken together, our study provides novel evidences to support that NDC80 is not only a promising clinical biomarker but also a potential therapeutical target for CRC precise medicine.

SUBMITTER: Yan X

PROVIDER: S-EPMC5806104 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nuclear division cycle 80 promotes malignant progression and predicts clinical outcome in colorectal cancer.

Yan Xuebing X Huang Linsheng L Liu Liguo L Qin Huanlong H Song Zhenshun Z

Cancer medicine 20180117 2

Colorectal cancer (CRC) is a common human malignancy worldwide and increasing studies have attributed its malignant progression to abnormal molecular changes in cancer cells. Nuclear division cycle 80 (NDC80) is a newly discovered oncoprotein that regulates cell proliferation and cycle in numerous malignancies. However, its clinical significance and biological role in CRC remain unclear. Therefore, in this study, we firstly analyze its expression in a retrospective cohort enrolling 224 CRC patie ...[more]

PMID: 29341479

Similar Datasets

Project description:BackgroundmiR-196b-5p expression is deregulated in many malignant tumors. Although miR-196b-5p has been implicated in the malignant transformation of colorectal cancer, its role in this specific type of cancer has not been fully explored. Thus, the present study was aimed to examine the cellular function of miR-196b-5p and its role in malignant biological behavior in colorectal cancer.MethodsmiR-196b-5p expression was measured in colorectal cancer tissues and cell lines using quantitative real-time PCR. Cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect proliferation, migration, and invasion in cell lines, whereas flow cytometry was applied to study apoptosis. Western blot analysis was performed to measure the protein levels. Dual luciferase reporter assay was used to investigate the interaction between miR-196b-5p and ING5. Tumor formation was evaluated in mice.ResultsMiR-196b-5p was abundantly expressed in colorectal cancer tissues and cell lines, whereas ING5 was expressed at low levels. MiR-196b-5p was successfully overexpressed or knocked down in colorectal cancer cells. We found that miR-196b-5p overexpression significantly accelerated the proliferation, cell cycle, migration and invasion, while inhibited cell apoptosis in colorectal cancer cells. However, miR-196b-5p inhibitor showed the opposite effects. Moreover, ING5 overexpression or knockdown was successfully performed in colorectal cancer cells. ING5 overexpression suppressed proliferation, migration, invasion, the phosphorylation of PI3K, Akt as well as MEK, and promoted cell apoptosis, which could be reversed by ING5 knockdown. Additionally, ING5 was identified as a target of miR-196b-5p through bioinformatics analysis and a luciferase activity assay. Furthermore, ING5 knockdown could attenuate the decrease in proliferation, migration, invasion, and the protein levels of p-PI3K, p-Akt, and p-MEK, which were induced by miRNA-196b-5p inhibitor. Besides, miR-196b-5p knockdown inhibited tumor growth, whereas ING5 knockdown elevated it in vivo.ConclusionsIn conclusion, miR-196b-5p promotes cell proliferation, migration, invasion, and inhibits apoptosis in colorectal cancer by targeting ING5.

Dataset Information

Nuclear division cycle 80 promotes malignant progression and predicts clinical outcome in colorectal cancer.

Publications

Nuclear division cycle 80 promotes malignant progression and predicts clinical outcome in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets