NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion

Jiang, Jingyi; Liu, Zheng; Ge, Chao; Chen, Cong; Zhao, Fangyu; Li, Hong; Chen, Taoyang; Yao, Ming; Li, Jinjun

doi:10.1074/jbc.m117.793760

Cited by 16 publications

(11 citation statements)

References 43 publications

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“…NKX3-1 negatively regulates the PI3K-AKT pathway to suppress tumor growth, and heterozygous deletions of NKX3-1 and PTEN cause prostate adenocarcinomas in mice ( Abate-Shen et al, 2003 ). Additionally, NKX3-1 functions as a tumor suppressor in hepatocellular carcinoma ( Jiang et al, 2017a ). In our analysis, increased NKX3-1 expression is strongly associated with poor overall survival ( P = 1.74 × 10 −4 ), and consistently higher expression is also found in prostate adenocarcinoma ( Fig.…”

Section: Emerging Targets In Glioblastomamentioning

confidence: 99%

Current Challenges and Opportunities in Treating Glioblastoma

et al. 2018

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Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and “druggable” targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates. Here, we review recent developments in GBM drug discovery and delivery. To identify GBM drug targets, we performed extensive bioinformatics analysis using data from The Cancer Genome Atlas project. We discovered 20 genes, BOC, CLEC4GP1, ELOVL6, EREG, ESR2, FDCSP, FURIN, FUT8-AS1, GZMB, IRX3, LITAF, NDEL1, NKX3-1, PODNL1, PTPRN, QSOX1, SEMA4F, TH, VEGFC, and C20orf166AS1 that are overexpressed in a subpopulation of GBM patients and correlate with poor survival outcomes. Importantly, nine of these genes exhibit higher expression in GBM versus low-grade glioma and may be involved in disease progression. In this review, we discuss these proteins in the context of GBM disease progression. We also conducted computational multi-parameter optimization to assess the blood-brain barrier (BBB) permeability of small molecules in clinical trials for GBM treatment. Drug delivery in the context of GBM is particularly challenging because the BBB hinders small molecule transport. Therefore, we discuss novel drug delivery methods, including nanoparticles and prodrugs. Given the aggressive nature of GBM and the complexity of targeting the central nervous system, effective treatment options are a major unmet medical need. Identification and validation of biomarkers and drug targets associated with GBM disease progression present an exciting opportunity to improve treatment of this devastating disease.

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Section: Emerging Targets In Glioblastomamentioning

confidence: 99%

Current Challenges and Opportunities in Treating Glioblastoma

et al. 2018

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“…ChIP assays were performed with SMMC-7721 and Hep3B cells as previously described. 33 Rabbit anti-EGR1 antibody (SC-189, Santa Cruz Biotechnology) or rabbit IgG were used to immunoprecipitate DNA-containing complexes. The isolated DNA samples were subjected to PCR analyses.…”

Section: Chromatin Immunoprecipitation Assay (Chip)mentioning

confidence: 99%

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

Li¹,

Chen²,

Ge³

et al. 2019

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Introduction: CD24 is known as a heavily glycosylated cell surface molecule that is highly expressed in a wide variety of human malignancies. Previous studies have shown that CD24 plays an important role in self-renewal, proliferation, migration, invasion and drug resistance of hepatocellular carcinoma (HCC). However, little is known about the expression and function of CD24 isoform a (CD24A) and CD24 isoform b (CD24B) in HCC. Materials and methods: Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were performed to detect CD24 and EGR1 expression in HCC cells and tissue. The function of CD24 in cell proliferation was verified with MTT assays, colony formation assays and tumor xenograft models. Wound healing assays and invasion assays were performed to clarify the function of CD24 in the regulation of cell migration and invasion in HCC. A dual luciferase reporter assay and chromatin immunoprecipitation assay were used to analyze the regulation mechanism of CD24A. Results: CD24A but not CD24B, which was barely detected by qPCR and Western blotting, is significantly upregulated in HCC tissue. Both CD24A and CD24B contribute to HCC cell proliferation, migration and invasion, but CD24A is more effective than CD24B. EGR1 downregulates CD24A and exerts transcription-promoting activity on the CD24A promoter. Furthermore, EGR1 represses HCC cell proliferation via downregulation of CD24A. Conclusion: CD24A is the predominant CD24 isoform in HCC and plays a major role in cell proliferation, migration, and invasion. EGR1 can exert its antitumor effect through transcriptional downregulation of CD24A in HCC.

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“…Tumor proliferation and apoptosis plays an important role in the occurrence and development of HCC [ 4 ]. The researches have demonstrated that HCC proliferation and apoptosis are closely related to abnormal expression of oncogenes and tumor suppressor genes [ 5 , 6 ]. Therefore, identification of novel diagnostic markers and therapeutic targets in HCC are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation

Liu

Wei

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe sperm-associated antigen 5 (SPAG5) plays a key role in controlling various cellular phenomena, including cell cycle progression and proliferation. However, the role of SPAG5 in hepatocellular carcinoma (HCC) remains unknown.MethodsThis study investigated the function and clinical significance of SPAG5 protein expression in hepatocellular carcinoma. We analyzed SPAG5 expression in surgical specimens from 136 HCC patients. The correlation between the clinical characteristics and prognosis was also determined. Furthermore, the SPAG5 was overexpressed in HCC cell and silenced with shRNA in HCC cells. Moreover, cell proliferation and apoptosis were measured using Edu assay and flow cytometry and a molecular mechanism of SPAG5 promotes HCC progression was explored.ResultsHerein, our study showed that upregulation of SPAG5 was detected frequently in primary HCC tissues, and was associated with significantly worse survival among the HCC patients. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of HCC. SPAG5 silence effectively abolished the proliferation abilities of SPAG5 in vivo and in vitro, while induced apoptosis in HCC cells. Furthermore, our results indicate that SPAG5 promoted cell progression by decreasing SCARA5 expression, which has been reported to control the progression of HCC, and our data demonstrated that SCARA5 is crucial for SPAG5-mediated HCC cell progression in vitro and in vivo. Moreover, we found that the expression of SPAG5 and SCARA5 are inversely correlated in HCC tissues. In addition, we demonstrated that SPAG5 promoted progression in HCC via downregulating SCARA5 depended on the β-catenin/TCF4 signaling pathway. Interestingly, the underlying mechanism is which SPAG5 regulates SCARA5 expression by modulating β-catenin degradation.ConclusionsTaken together, our data provide a novel evidence for the biological and clinical significance of SPAG5 as a potential biomarker, and we demonstrate that SPAG5-β-catenin-SCARA5 might be a novel pathway involved in HCC progression.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0891-3) contains supplementary material, which is available to authorized users.

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NK3 homeobox 1 (NKX3.1) up-regulates forkhead box O1 expression in hepatocellular carcinoma and thereby suppresses tumor proliferation and invasion

Cited by 16 publications

References 43 publications

Current Challenges and Opportunities in Treating Glioblastoma

Current Challenges and Opportunities in Treating Glioblastoma

<p>CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma</p>

SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation

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