SPINK1 promotes cell growth and metastasis of lung adenocarcinoma and acts as a novel prognostic biomarker

Xu, Lixiang; Lu, Changchang; Huang, Ying; Zhou, Ji; Wang, Xincheng; Liu, Chaowu; Chen, Jun; Le, Hanh

doi:10.5483/bmbrep.2018.51.12.205

Cited by 54 publications

(44 citation statements)

References 25 publications

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“…Evidently, the expression of FUBP1 was commonly upregulated in several types of cancers as previously reported ( Figure 3 A). However, interestingly, gene profiling analysis comparing lung cancer and adjacent normal cell (GEO accession: GSE118370) [ 39 ] revealed that FUBP1 expression was significantly downregulated in lung adenocarcinoma, the most common lung cancer subtype among non-smokers and women ( Figure 3 B). In addition, we also used Gene Expression Profiling Interactive Analysis (GEPIA, ) [ 40 ] to look for differential gene expression and it was confirmed that the expression of FUBP1 was clearly reduced in both lung adenocarcinoma and lung squamous cell carcinoma tissues ( Figure 3 C), suggesting that FUBP1 would be less necessary in lung cancer development.…”

Section: Resultsmentioning

confidence: 99%

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Kang

Kim

et al. 2020

Cells

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The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named “double-agent” genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 “double-agent” genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.

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Section: Resultsmentioning

confidence: 99%

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Kang

Kim

et al. 2020

Cells

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“…Low expression of TAT was found in HCC, and downregulation of TAT promoted tumor progression [31]. Several previous studies revealed that SPINK1 is associated with various cancers development [32][33][34]. In HCC, researchers found the expression of SPINK1 was increased in tumor tissues by micro-arrays analysis, high level of SPINK1 promoted the proliferation, migration and invasion ability of HCC cells [33].…”

Section: Discussionmentioning

confidence: 97%

Identification of Key Genes and Evaluation of Their Prognosis Potential in Hepatocellular Carcinoma by Integrated Bioinformatics Analysis

Liu

et al. 2020

Preprint

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Abstract Background Hepatocellular carcinoma (HCC) is a malignancy causing highly death rate in the world. Despite the development of treatment strategies for HCC, prognosis of this malignancy remains unsatisfactory. In this study, we aimed to identify the target genes associated with the prognosis of HCC patients. Methods Three expression profiles of HCC tissues were extracted from the Gene Expression Omnibus database to explore the differentially expressed genes (DEGs) using GEO2R method. Functional enrichment analysis was performed to reveal the biological characteristics of DEGs. Protein-protein interaction (PPI) network was constructed using Cytoscape software. The survival curve of identified DEGs were tested by Kaplan-Meier analysis. Results We identified 15 DEGs (CYP39A1, CYR61, FOS, FOXO1, GADD45B, ID1, IL1RAP, MT1M, PHLDA1, RND3, SDS, SOCS2, TAT, S100P, and SPINK1) in HCC tissues. Prognosis analysis showed that 4 DEGs (FOXO1,SPINK1༌SOCS2, and TAT) correlated with overall survival time of HCC patients, which might serve as therapeutic targets for HCC patients. Conclusions By integrated bioinformatics analysis, we proposed a novel way to reveal key genes that closely relate to HCC development.

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“…Among the predicted pathways, SPINK1-metallothionein signaling was the top pathway with a significant correlation ( Figure 2C,D). The aberrant activation of SPINK1 signaling could contribute to tumor malignancy, including increased invasion and proliferation of tumor cells [13][14][15]. Both SPINK1 and the metallothionein gene family, including MT1F, MT1G, MT1H, and MT3, were downregulated in the comparison of DDX3X high versus DDX3X low (Figure 2E), suggesting DDX3X's critical role in repressing RCC progression.…”

Section: Knowledge-based Transcriptomic Analysis Revealed That the Spmentioning

confidence: 99%

DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression

Lin

2020

IJMS

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DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, DDX3X’s role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to DDX3X. The results suggest that DDX3X is epigenetically repressed in tumor tissue and that lower DDX3X is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by DDX3X. Furthermore, SPINK1 and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with DDX3X in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low DDX3X. Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3Xlow/SPINK1high/metallothioneinhigh axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low DDX3X expression levels.

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SPINK1 promotes cell growth and metastasis of lung adenocarcinoma and acts as a novel prognostic biomarker

Cited by 54 publications

References 25 publications

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Identification of Key Genes and Evaluation of Their Prognosis Potential in Hepatocellular Carcinoma by Integrated Bioinformatics Analysis

DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression

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