Correlation of NUF2 Overexpression with Poorer Patient Survival in Multiple Cancers
Autor: | Qing-Zhe Dong, Shenling Li, Fengyun Hao, Amudha Deivasigamani, Nian-Kai Zhang, Brian K. P. Goh, Kam M. Hui, Yu Wang, Karthik Sekar, Yan Jiang, Clara Kai Ting Koh, London L.P.J. Ooi, Senbiao Luo, Xiao-Dan Jiang |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Cancer Research Disease-free survival Mice Nude Pan-cancer Apoptosis Cell Cycle Proteins NUF2 Cell cycle medicine.disease_cause Mice 03 medical and health sciences 0302 clinical medicine In vivo Neoplasms Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Gene silencing Overall survival General Cell Proliferation Gene knockdown business.industry Cancer Middle Aged Prognosis medicine.disease Xenograft Model Antitumor Assays In vitro Gene Expression Regulation Neoplastic Survival Rate 030104 developmental biology Oncology 030220 oncology & carcinogenesis Hepatocellular carcinoma Cancer research Original Article Female Carcinogenesis business |
Zdroj: | Cancer Research and Treatment : Official Journal of Korean Cancer Association |
ISSN: | 2005-9256 1598-2998 |
DOI: | 10.4143/crt.2020.466 |
Popis: | Purpose NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). Materials and methods RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma cell lines was used to evaluate NUF2's role in hepatocellular carcinoma (HCC) in vitro and in vivo. Results NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 μm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. Conclusion NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies. |
Databáze: | OpenAIRE |
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