Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation

Mazloomian, Alborz; Araki, Shinsuke; Ohori, Momoko; El-Naggar, Amal M.; Yap, Damian; Bashashati, Ali; Nakao, Shigetomi; Sorensen, Poul H.; Nakanishi, Atsushi; Shah, Sohrab P.; Aparicio, Samuel

doi:10.1038/s42003-019-0391-9

Cited by 32 publications

(33 citation statements)

References 59 publications

(79 reference statements)

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“…Previous studies have reported that EIF4A3 is a key component of cell cycle and apoptosis regulation (20)(21)(22)(23). In addition, EJC-related components serve a vital role in the splicing of apoptosis factor mRNA.…”

Section: Eif4a3 and Cell Functionmentioning

confidence: 99%

“…Lin et al (28) demonstrated that EIF4A3 expression is upregulated in HCC tissues compared with healthy liver tissues, and high EIF4A3 expression is associated with a poor prognosis. EIF4A3 is strongly associated with the expression of several types of cell cycle regulatory genes (CDK1 and CDK2), tumor-associated transcription factors, chemokine signaling pathways and spliceosome signaling pathways (18,(20)(21)(22). In addition, EIF4A3 expression is upregulated in ovarian cancer tissues compared with adjacent healthy ovarian tissues (23).…”

Section: Eif4a3 and Tumorsmentioning

confidence: 99%

“…Furthermore, EIF4A3 serves a role in cell cycle monitoring. Inhibition of EIF4A3 using compounds or gene interference technology decreases cell cycle arrest in the G 2 /M phase, which in turn increases apoptosis ( 21 ).…”

Section: Eif4a3 and Cell Functionmentioning

confidence: 99%

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Effect of eukaryotic translation initiation factor 4A3 in malignant tumors (Review)

Zhu

Ren

2021

Oncol Lett

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Eukaryotic translation initiation factor 4A3 (EIF4A3), a key component of the exon junction complex, is widely involved in RNA splicing and nonsense-mediated mRNA decay. EIF4A3 has also been reported to be involved in cell cycle regulation and apoptosis. Thus, EIF4A3 may serve as a pivotal regulatory factor involved in the occurrence and development of multiple diseases. Previous studies have demonstrated that EIF4A3 is mutated in neuromuscular degenerative lesions and is differentially expressed in several tumors, serving as a non-coding RNA binding protein to regulate its expression. In addition, studies have reported that inhibiting EIF4A3 can prevent tumor cell proliferation, thus, several researchers are trying to design and synthesize potent and selective EIF4A3 inhibitors. The present review summarizes the function of EIF4A3 in cell cycle and discusses it underlying molecular mechanisms that contribute to the occurrence of malignant diseases. In addition, EIF4A3 selective inhibitors, and bioinformatics analyses performed to analyze the expression and mutations of EIF4A3 in gynecological tumors and breast cancer, are also discussed.

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Section: Eif4a3 and Cell Functionmentioning

confidence: 99%

Section: Eif4a3 and Tumorsmentioning

confidence: 99%

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Effect of eukaryotic translation initiation factor 4A3 in malignant tumors (Review)

Zhu

Ren

2021

Oncol Lett

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“…26 Soon after, Krackhardt et al 27 and Scanlan et al 28 found that there was an obvious binding reaction between RBM38 antigen and the serum from patients with leukemia and colon cancer. In the following study of Chen et al, RBM38 was found to be induced by p53 family and acted as a potential common target of the p53 family, 29 which was later verified by Shu et al 30 Due to its regulatory role in the stability of various mRNAs and the correlation between p53 family and tumors, RBM38 was speculated to be a tumorrelated gene, which was confirmed in subsequent studies.…”

Section: The History Of Rbm38mentioning

confidence: 79%

RNA-Binding Motif Protein 38 as a Potential Biomarker and Therapeutic Target in Cancer

She¹,

Lin²,

Liang³

et al. 2020

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RNA-binding proteins (RBPs) act as a key factor in gene regulation by governing RNA metabolism. They contribute to the expression and functions of most RNAs by binding to them and forming complexes. RNA-binding motif protein 38 (RBM38), a member of the RBP family, alters the stability and translation of targeted mRNAs to affect various biological processes, such as cell proliferation, cell cycle arrest, and myogenic differentiation. RBM38 contains a highly conserved RNA recognition motif (RRM) consisting of two subunits, RNP1 and RNP2, which specifically bind to RNAs. Recent studies have revealed that RBM38 regulates the mRNA stability of several tumor-related genes, such as p53 , mdm2 , p63 , p73 , p21 , and c-Myc , by binding to their 3′ untranslated regions (3′ UTRs); thus, RBM38 modulates targeted gene expression and affects the biological processes of tumors. In addition, abnormal RBM38 expression in some malignant tumors and its correlation with prognosis have been documented in many studies, indicating its value for potential clinical applications. In this review, we present an overview of RBM38, specifically highlighting its relationship with tumor manifestation and development. A brief overview of the potential use of RBM38 in cancer therapy is also included to provide ideas for further research on RBM38.

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“…EIF4A3 is a key component of the exon junction complex (EJC), and its assembly is associated with splicing ( Sauliere et al, 2012 ). In cancer cells, EIF4A3 is associated with posttranscriptional modification, cell cycle progression, and acceleration of cell growth ( Han et al, 2016 ; Mazloomian et al, 2019 ; Zheng et al, 2020 ). Especially in HCC, EIF4A3 is regarded as one of the important phosphoproteins in HCC metastasis ( Tian et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Systemic Expression Analysis Reveals Prognostic Significance of WIPI3 in Hepatocellular Carcinoma

et al. 2020

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Introduction: WD repeat domain phosphoinositide-interacting protein 3 (WIPI3) is a member of the WIPI protein family, autophagy marker, that is associated with the malignant progression of various human cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. Materials and Methods: Firstly, we collected the mRNA expression of WIPI3 in HCC through the platform of Oncomine, as well as the DNA copy number variations (CNVs), and verified it on human HCC cell line and the GEO database. Then, the subgroups and prognosis of HCC were performed by the UALCAN web tool. The mutation of WIPI3 was analyzed by cBioPortal. The coexpression of WIPI3 in HCC was identified from the LinkedOmics database, and function enrichment analysis was done using the LinkFinder module in LinkedOmics. Coexpression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules; both of them were visualized by the Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) by using the UCSC Xena browser. Results: The results indicated that WIPI3 was frequently overexpressed in HCC, which could lead to a poor prognosis through the Kaplan-Meier (KM) analysis. Moreover, there existed mutations of WIPI3 in HCC, and the prognosis of WIPI3-altered group was significantly poor based on KM plotter data. Coexpression analysis showed that the coexpression gene of WIPI3 was associated with cell cycle and spliceosome. Further analysis suggested that WIPI3 and eukaryotic translation initiation factor 4A3 (EIF4A3) coordinately regulated the cancer cell cycle by spliceosome as a result of the strong positive correlation between them. Conclusion: In summary, WIPI3 is constantly overexpressed in HCC tissues, resulting in a poor prognosis; therefore, we can identify it as an effective target for the treatment of HCC.

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Pharmacological systems analysis defines EIF4A3 functions in cell-cycle and RNA stress granule formation

Cited by 32 publications

References 59 publications

Effect of eukaryotic translation initiation factor 4A3 in malignant tumors (Review)

Effect of eukaryotic translation initiation factor 4A3 in malignant tumors (Review)

RNA-Binding Motif Protein 38 as a Potential Biomarker and Therapeutic Target in Cancer

Systemic Expression Analysis Reveals Prognostic Significance of WIPI3 in Hepatocellular Carcinoma

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