Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas

Liu, Qiang; Dai, Shejiao; Li, Hong; Li, Dong; Peng, Yu‐Ping

doi:10.7314/apjcp.2014.15.20.8623

Cited by 42 publications

(40 citation statements)

References 33 publications

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“…15 Here, we further demonstrated the high NUF2 expression is significantly associated with poorer HCC patient survival, and NUF2 is a promising prognostic biomarker to accurately predict early HCC recurrence postsurgical resection. We further evaluated the prognostic biomarker potential of the transcriptome signature in an independent cohort and identified NUF2 as a promising biomarker to predict HCC early recurrence.…”

Section: Introductionmentioning

confidence: 56%

“…Previous evidence demonstrated that NUF2 promotes cell growth and inhibits apoptosis in HCC cells. 15 Here, we further demonstrated the high NUF2 expression is significantly associated with poorer HCC patient survival, and NUF2 is a promising prognostic biomarker to accurately predict early HCC recurrence postsurgical resection.…”

Section: Introductionmentioning

confidence: 56%

“…ANLN has been reported to be associated with poorer prognosis in breast, 28 bladder 29 and colorectal cancers 30 while BIRC5, KIF23 and NUF2 have been reported to be functionally important for HCC cell growth. 15,31,32 Multivariate logistic regression identified NUF2 as the minimal biomarker sufficient to predict HCC early recurrence (Fig. 2b).…”

Section: Discussionmentioning

confidence: 99%

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NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Wang

Tan

Handoko

et al. 2019

Intl Journal of Cancer

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Early tumor recurrence after curative surgical resection poses a great challenge to the clinical management of hepatocellular carcinoma (HCC). We conducted whole genome expression microarrays on 64 primary HCC tumors with clinically defined recurrence status and cross‐referenced with RNA‐seq data from 18 HCC tumors in the Cancer Genome Atlas project. We identified a 77‐gene signature, which is significantly associated with early recurrent (ER) HCC tumors. This ER‐associated signature shows significant enrichment in genes involved in cell cycle pathway. We performed receiver operating characteristic (ROC) analysis to evaluate the prognostic biomarker potential of these 77 genes and Pearson correlation analysis to identify 11 close clusters. The one gene with the best area under the ROC curve in each of the 11 clusters was selected for validation using reverse‐transcription quantitative PCR in an independent cohort of 24 HCC tumors. NUF2 was identified to be the minimal biomarker sufficient to discriminate ER tumors from LR tumors. NUF2 in combination with liver cirrhosis could significantly improve the detection of ER tumors with an AUROC of 0.82 and 0.85 in the test and validation cohort, respectively. In conclusion, NUF2 in combination with liver cirrhosis is a promising prognostic biomarker for early HCC recurrence.

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Section: Introductionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Wang

Tan

Handoko

et al. 2019

Intl Journal of Cancer

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“…For example, elevated NUF2 gene expression has been found in a range of tumor types and cell lines (23)(24)(25)(26) and is associated with poor outcome in cancer patients (23,25). Furthermore, silencing of NUF2 inhibits tumor growth and leads to apoptosis in cancer cell lines (23)(24)(25)(26)(27)(28), likely induced by the spindle checkpoint pathway (22). Experimental follow-up is required to ultimately understand the role of the clustered NUF2 mutations in cancer.…”

Section: Significancementioning

confidence: 99%

Comprehensive assessment of cancer missense mutation clustering in protein structures

Kamburov

Lawrence

Polak

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

206

226

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Large-scale tumor sequencing projects enabled the identification of many new cancer gene candidates through computational approaches. Here, we describe a general method to detect cancer genes based on significant 3D clustering of mutations relative to the structure of the encoded protein products. The approach can also be used to search for proteins with an enrichment of mutations at binding interfaces with a protein, nucleic acid, or small molecule partner. We applied this approach to systematically analyze the PanCancer compendium of somatic mutations from 4,742 tumors relative to all known 3D structures of human proteins in the Protein Data Bank. We detected significant 3D clustering of missense mutations in several previously known oncoproteins including HRAS, EGFR, and PIK3CA. Although clustering of missense mutations is often regarded as a hallmark of oncoproteins, we observed that a number of tumor suppressors, including FBXW7, VHL, and STK11, also showed such clustering. Beside these known cases, we also identified significant 3D clustering of missense mutations in NUF2, which encodes a component of the kinetochore, that could affect chromosome segregation and lead to aneuploidy. Analysis of interaction interfaces revealed enrichment of mutations in the interfaces between FBXW7-CCNE1, HRAS-RASA1, CUL4B-CAND1, OGT-HCFC1, PPP2R1A-PPP2R5C/PPP2R2A, DICER1-Mg 2+ , MAX-DNA, SRSF2-RNA, and others. Together, our results indicate that systematic consideration of 3D structure can assist in the identification of cancer genes and in the understanding of the functional role of their mutations.cancer | cancer genetics | mutation clustering | protein structures | interaction interfaces

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“…Both of these proteins are known cancer drug targets and are now being considered as crucial molecules in the development of tumor-agnostic drugs to treat diverse cancer types 45 . Silencing of the NUF2 protein has been shown to hinder tumor growth across cancer types 46 www.nature.com/scientificreports www.nature.com/scientificreports/ NTRK1 protein has been successfully targeted by the drug Entrectinib 48 . Our results, therefore, suggest that the drug Entrectinib may be a choice in the treatment regimen of a diverse number of cancer types but may not be beneficial to patients diagnosed with STES, BLCA, LUSC (apart from ROS1-positive) and PRAD.…”

Section: Resultsmentioning

confidence: 99%

Edgetic perturbation signatures represent known and novel cancer biomarkers

Kataka

Zaucha

Frishman

et al. 2020

Sci Rep

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isoform switching is a recently characterized hallmark of cancer, and often translates to the loss or gain of domains mediating protein interactions and thus, the re-wiring of the interactome. Recent computational tools leverage domain-domain interaction data to resolve the condition-specific interaction networks from RnA-Seq data accounting for the domain content of the primary transcripts expressed. Here, we used The Cancer Genome Atlas RNA-Seq datasets to generate 642 patient-specific pairs of interactomes corresponding to both the tumor and the healthy tissues across 13 cancer types. The comparison of these interactomes provided a list of patient-specific edgetic perturbations of the interactomes associated with the cancerous state. We found that among the identified perturbations, select sets are robustly shared between patients at the multi-cancer, cancer-specific and cancer subtype specific levels. Interestingly, the majority of the alterations do not directly involve significantly mutated genes, nevertheless, they strongly correlate with patient survival. The findings (available at edgeexplorer: "http://webclu.bio.wzw.tum.de/edgeexplorer") are a new source of potential biomarkers for classifying cancer types and the proteins we identified are potential anti-cancer therapy targets.Cancer involves the accumulation of somatic mutations 1 and epigenetic modifications 2 , which drive the cells into the malignant state. Recurrent mutations implicated in tumorigenesis affect highly connected proteins within the protein interaction network 3,4 and are enriched at the interaction interfaces 5,6 and phosphorylation sites 7 signifying their role in rewiring protein interactions 8 . For this reason, cancer has been described as the disease of the interactome 9 . Indeed, the network of protein-protein interactions (PPI) has repeatedly allowed for the extraction of molecular features predictive of various phenotypic traits relevant to cancer -the so-called disease biomarkers 10 . For example, Cui et al. have identified putative interaction-disrupting mutations occurring at the interfaces of protein complexes and demonstrated that their presence is prognostic of poor survival 11 . In another study, Li et al. 12 developed the "OncoPPI" network of protein-protein interactions (PPIN) relevant to lung cancer, identifying biomarkers that can inform therapeutic decisions according to the drug sensitivity in certain conditions 12 . Nevertheless, the physical disruption of interaction sites by somatic mutations is only one mode of perturbing the interactome. Another relevant cellular process is regulating the expression (and thereby the local molecular concentration) of the interacting proteins 13 ; this has been utilized in mining the network of protein-protein interactions to identify modules of differentially expressed genes serving as robust biomarkers indicative of breast cancer metastasis 14 or stratifying patients from several breast cancer subtypes 15 . Furthermore, the phenomenon of "isoform switching", i.e. altering t...

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Silencing of NUF2 Inhibits Tumor Growth and Induces Apoptosis in Human Hepatocellular Carcinomas

Cited by 42 publications

References 33 publications

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

NUF2 is a valuable prognostic biomarker to predict early recurrence of hepatocellular carcinoma after surgical resection

Comprehensive assessment of cancer missense mutation clustering in protein structures

Edgetic perturbation signatures represent known and novel cancer biomarkers

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