scholarly journals The Protein Expression of PDL1 Is Highly Correlated with Those of eIF2α and ATF4 in Lung Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Liang-Che Chang ◽  
Tzu-Ping Chen ◽  
Wei-Ke Kuo ◽  
Chung-Ching Hua
Keyword(s):  
Lung Cancer ◽  
Protein Level ◽  
Cell Function ◽  
Immune Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Tumor Tissues ◽  
Programmed Death

Introduction. The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFNα. The eIF2α/ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment. Materials and Methods. The protein levels of PDL1, IRF1, IRF7, STAT1, STAT2, IFNAR1, eIF2α, and ATF4 in the normal and tumor tissues of 27 subjects with lung cancer were determined by Western blot. Results. The protein level of PDL1 was significantly correlated with those of IRF1, eIF2α, and ATF4 in the tissues of all subjects and the subgroup of squamous cell carcinoma but not in the normal tissue of adenocarcinoma. The protein levels of IRF1, eIF2α, and ATF4 were consistently correlated in the tumor tissues but to various extents in the normal ones. The protein level of PDL1 was not correlated with those of STAT1 and STAT2 in all the tissues. Conclusion. The PDL1 expression in lung cancer may be independent of STAT1 and STAT2. The PD1/PDL1 axis and UPR/ISR may be closely associated in the tumor tissues of lung cancer.

scholarly journals The Cap-Binding Complex CBC and the Eukaryotic Translation Factor eIF4E: Co-Conspirators in Cap-Dependent RNA Maturation and Translation

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6185
Author(s):  
Jean-Clement Mars ◽  
Mehdi Ghram ◽  
Biljana Culjkovic-Kraljacic ◽  
Katherine L. B. Borden
Keyword(s):  
Nuclear Export ◽  
Mammalian Cells ◽  
Physical Nature ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Cap Binding Complex ◽  
Rna Maturation

The translation of RNA into protein is a dynamic process which is heavily regulated during normal cell physiology and can be dysregulated in human malignancies. Its dysregulation can impact selected groups of RNAs, modifying protein levels independently of transcription. Integral to their suitability for translation, RNAs undergo a series of maturation steps including the addition of the m7G cap on the 5′ end of RNAs, splicing, as well as cleavage and polyadenylation (CPA). Importantly, each of these steps can be coopted to modify the transcript signal. Factors that bind the m7G cap escort these RNAs through different steps of maturation and thus govern the physical nature of the final transcript product presented to the translation machinery. Here, we describe these steps and how the major m7G cap-binding factors in mammalian cells, the cap binding complex (CBC) and the eukaryotic translation initiation factor eIF4E, are positioned to chaperone transcripts through RNA maturation, nuclear export, and translation in a transcript-specific manner. To conceptualize a framework for the flow and integration of this genetic information, we discuss RNA maturation models and how these integrate with translation. Finally, we discuss how these processes can be coopted by cancer cells and means to target these in malignancy.

scholarly journals Genetic Variability in eIF2α Gene Is Associated with Islet β-Cell Function in the Development of Diabetes in a Chinese Han Population

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Nan Gu ◽  
Xiaowei Ma ◽  
Jianwei Zhang ◽  
Mengmeng Jin ◽  
Nan Feng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Function ◽  
Tolerance Test ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Oral Glucose ◽  
Genotype Distribution ◽  
Chinese Han ◽  
Eukaryotic Translation ◽  
Β Cell Function

Aims. Protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2α) pathway mutations lead to failure of β-cell function. The aim of this article was to assess the association between eIF2α and the risk of glucose metabolism abnormalities. Methods. Two eIF2α SNPs (rs9840992 T>C and rs13072593 A>G) were selected based on CHB data from HapMap, and 1466 unrelated nondiabetes individuals were genotyped. All subjects were examined by the 75 g oral glucose tolerance test, and 733 participated in a subsequent insulin release test. Various indicators of insulin resistance and islet β-cell function were examined. Results. There were no significant differences in genotype distribution and allele frequency between the prediabetes and controls. CC genotype carriers at rs9840992 showed higher insulin levels at 120 min after a 75 g glucose load than noncarriers. Also, CC homozygotes had higher ΔI30/ΔG30 and ΔI120/ΔG120 than noncarriers, even after adjusting for insulin resistance. CC homozygotes had greater AUCi values than noncarriers. Subjects aged ≥ 65 yrs, those with a BMI ≥ 24 kg/m2 and those carrying the rs9840992 risk allele, had a 2.5-fold higher risk of glucose abnormalities than subjects who had none of these risk factors. Conclusion. The eIF2α polymorphism is associated with islet β-cell function in a Chinese population.

scholarly journals miR-133a acts as a tumor suppressor in colorectal cancer by targeting eIF4A1

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769838 ◽  
Author(s):  
Wenfeng Li ◽  
Anqi Chen ◽  
Lingling Xiong ◽  
Ting Chen ◽  
Fengxing Tao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Translation Initiation ◽  
Colon Cancer Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Tumor Tissues ◽  
Colon Cancer Cell Lines ◽  
Eukaryotic Translation Initiation ◽  
Direct Target

Emerging evidence indicates that microRNAs play critical roles in carcinogenesis and cancer progression. In this study, miR-133a was found to be significantly downregulated in colon tumor tissues. We aimed to determine its biological function, molecular mechanisms, and direct target genes in colorectal cancer. From these results, we found that miR-133a was significantly downregulated in primary tumor tissues and colon cancer cell lines. Ectopic expression of miR-133a in colon cancer cell lines significantly suppressed cell growth, as evidenced by cell viability and colony formation assays, as well as reduced xenograft tumor growth in nude mice. However, the effect of miR-133a was abolished by the overexpression of eIF4A1. Moreover, miR-133a inhibited cellular migration and invasiveness. A luciferase activity assay revealed oncogene eukaryotic translation initiation factor 4A1 as a direct target gene of miR-133a, whose expression was inversely correlated with that of miR-133a. Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer.

scholarly journals The exon junction complex core factor eIF4A3 is a key regulator of HPV16 gene expression

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Koceila Meznad ◽  
Philippe Paget-Bailly ◽  
Elise Jacquin ◽  
Anne Peigney ◽  
François Aubin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Exon Junction Complex ◽  
Eukaryotic Translation ◽  
Protein Levels ◽  
Exon Junction ◽  
Complex Core ◽  
Eukaryotic Translation Initiation ◽  
E6 And E7

Abstract High-risk human papillomavirus (hrHPVs), particularly HPV16 and HPV18, are the etiologic factors of ano-genital cancers and some head and neck squamous cell carcinomas (HNSCCs). Viral E6 and E7 oncoproteins, controlled at both transcriptional and post-transcriptional levels, drive hrHPVs-induced carcinogenesis. In the present study, we investigated the implication of the DEAD-box helicase eukaryotic translation initiation factor 4A3 (eIF4A3,) an Exon Junction Complex factor, in the regulation of HPV16 gene expression. Our data revealed that the depletion of the factor eIF4A3 up-regulated E7 oncoprotein levels. We also showed that the inhibition of the nonsense-mediated RNA decay (NMD) pathway, resulted in the up-regulation of E7 at both RNA and protein levels. We therefore proposed that HPV16 transcripts might present different susceptibilities to NMD and that this pathway could play a key role in the levels of expression of these viral oncoproteins during the development of HPV-related cancers.

Interfering Eukaryotic Translation Initiation Factor 3 Subunit J Antisense RNA1 Inhibits the Proliferation, Migration, and Invasion of Lung Cancer A549 Cells by Regulating microRNA-330-5p

2020 ◽  
Vol 12 (9) ◽  
pp. 1099-1105
Author(s):  
Li Wei ◽  
Lijun Liu ◽  
Lin Chen ◽  
Xiaoning Li ◽  
Zaiyan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Noncoding Rna ◽  
A549 Cells ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Migration And Invasion ◽  
Eukaryotic Translation ◽  
Eukaryotic Translation Initiation ◽  
Cancer Tissues

This study investigated whether long noncoding RNA interfering EIF3J antisense RNA1 (EIF3JAS1) could affect lung cancer A549 cells as well as the role of microRNA-330-5p (miR-330-5p) during this process. To this end, quantitative real-time polymerase chain reaction was used to measure EIF3J-AS1 and miR-330-5p expression in 39 lung cancer cases. Small interfering RNA targeting EIF3J-AS1 (si-EIF3J-AS1), as well as the miR-330-5p inhibitor, was transfected into lung cancer A549 cells. The outcomes of cell proliferation, clone formation, migration, invasion, and E- and N-cadherin expression were analyzed using CCK-8 kit, clone formation experiment, Transwell method, and Western blot. The targeted binding between EIF3J-AS1 and miR-330-5p was explored using the luciferase experiment. The results showed higher EIF3J-AS1 expression but lower miR-330-5p expression cancer tissues. Furthermore, interfering EIF3J-AS1 increased miR-330-5p and E-cadherin protein expression, leading to a reduction in the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells. Meanwhile, Transfecting si-EIF3J-AS1 and the miR-330-5p inhibitor could increase the proliferation, clone formation, migration, invasion, and N-cadherin protein expression of lung cancer A549 cells, suggesting the targeted relationship of EIF3J-AS1 to miR-330-5p. In summary, EIF3J-AS1 was highly expressed in lung cancer tissues, and interfering EIF3J-AS1 inhibited the proliferation,migration, and invasion of A549 cells through negative regulation of miR-330-5p.

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