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 metaanalysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA).
Materials and MethodsRNA-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.
ResultsNUF2 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.
ConclusionNUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.
As one of the major causes of cancer-related death, gastrointestinal cancer seriously impacts the quality of human life. Moreover, in the majority of patients, the disease is in an advanced state at the time of diagnosis. The only available treatment for such patients is systemic chemotherapy, which may cause various side effects. Thus, the need for fast evaluation functions of different medicines and developing new drugs have become urgent in recent years. In this study, four different anti-cancer reagents, namely, compound Kushen injection (CKI), cinobufacini injection, transforming growth factor-β1 (TGF-β1), and 5-fluorouracil (5-FU), were each tested with a cell-based biosensor to investigate their therapeutic effects on gastrointestinal cancer cells. From the impedance results, we could infer that chemotherapeutic agents could induce cell apoptosis, disrupt cell cycle, and inhibit cell adhesion capacity. By combining impedance spectra with an appropriate impedance circuit, the function of 5-FU on cell death and adhesion could be preliminarily investigated. Because the impedance sensing is in real time, has high throughput, and is easily manipulated, the developed cell-based impedance biosensor could be used as a suitable and promising alternative to end-point assay in the preclinical research of medicines, including the development of new therapeutic regimens.
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